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Taieb A, Asma G, Jabeur M, Fatma BA, Nassim BHS, Asma BA. Rethinking the Terminology: A Perspective on Renaming Polycystic Ovary Syndrome for an Enhanced Pathophysiological Understanding. Clin Med Insights Endocrinol Diabetes 2024; 17:11795514241296777. [PMID: 39494232 PMCID: PMC11528641 DOI: 10.1177/11795514241296777] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2024] [Accepted: 10/16/2024] [Indexed: 11/05/2024] Open
Abstract
Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder that affects women at various stages of life, presenting a wide range of symptoms and health implications. The term "Polycystic Ovary Syndrome" can be misleading, prompting many within the medical community and advocacy groups to advocate for a name change. Critics argue that this terminology can complicate understanding and awareness of the disease among patients. The primary concern is that PCOS emphasizes the ovarian aspect, fostering the misconception that PCOS is merely a gynecological disorder. In reality, PCOS impacts multiple organ systems, particularly metabolic health. Patients frequently experience insulin resistance, weight gain, irregular menstrual cycles, and hirsutism-symptoms that extend beyond ovarian dysfunction. In light of these issues, there is increasing support for renaming PCOS to better reflect its systemic implications and minimize confusion. The current name may hinder understanding and potentially lead to inadequate disease management. Alternative names have been proposed, including "Ovarian Dysmetabolic Syndrome," which our team supports, as well as "Metabolic Reproductive Syndrome" and "Hyperandrogenic Persistent Ovulatory Dysfunction Syndrome." These alternatives aim to highlight the hormonal imbalances and metabolic disturbances associated with the condition, fostering inclusivity and reducing stigma for all affected individuals. This narrative review provides a historical overview of PCOS, tracing its recognition from early descriptions to contemporary guidelines. We discuss the evolving understanding of its pathophysiology and the rationale behind the proposed name change. By adopting a new nomenclature, we can enhance understanding among healthcare professionals, increase inclusivity for affected women, reduce the stigma and anxiety linked to the diagnosis, and offer a more accurate representation of the condition's complex pathophysiology.
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Affiliation(s)
- Ach Taieb
- Department of Endocrinology, University Hospital of Farhat Hached Sousse, Tunisia
- University of Sousse, Faculty of Medicine of Sousse, Sousse, Tunisia
- Laboratory of Exercise Physiology and Pathophysiology; L.R, Sousse, Tunisia
| | - Gorchane Asma
- Department of Endocrinology, University Hospital of Farhat Hached Sousse, Tunisia
- University of Sousse, Faculty of Medicine of Sousse, Sousse, Tunisia
| | - Methnani Jabeur
- University of Sousse, Faculty of Medicine of Sousse, Sousse, Tunisia
- Laboratory of Exercise Physiology and Pathophysiology; L.R, Sousse, Tunisia
| | - Ben Abdessalem Fatma
- Department of Endocrinology, University Hospital of Farhat Hached Sousse, Tunisia
- University of Sousse, Faculty of Medicine of Sousse, Sousse, Tunisia
| | - Ben Haj Slama Nassim
- Department of Endocrinology, University Hospital of Farhat Hached Sousse, Tunisia
- University of Sousse, Faculty of Medicine of Sousse, Sousse, Tunisia
| | - Ben Abdelkrim Asma
- Department of Endocrinology, University Hospital of Farhat Hached Sousse, Tunisia
- University of Sousse, Faculty of Medicine of Sousse, Sousse, Tunisia
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Chang KJ, Chen JH, Chen KH. The Pathophysiological Mechanism and Clinical Treatment of Polycystic Ovary Syndrome: A Molecular and Cellular Review of the Literature. Int J Mol Sci 2024; 25:9037. [PMID: 39201722 PMCID: PMC11354688 DOI: 10.3390/ijms25169037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Revised: 08/07/2024] [Accepted: 08/10/2024] [Indexed: 09/03/2024] Open
Abstract
Polycystic ovary syndrome (PCOS) is a prevalent metabolic disorder among women of reproductive age, characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries. The pathogenesis of PCOS involves a complex interplay of genetic and environmental factors, including insulin resistance (IR) and resultant hyperinsulinemia. Insulin receptors, primarily in skeletal muscle, liver, and adipose tissue, activate downstream signaling pathways like PI3K-AKT and MAPK-ERK upon binding. These pathways regulate glucose uptake, storage, and lipid metabolism. Genome-wide association studies (GWASs) have identified several candidate genes related to steroidogenesis and insulin signaling. Environmental factors such as endocrine-disrupting chemicals and lifestyle choices also exacerbate PCOS traits. Other than lifestyle modification and surgical intervention, management strategies for PCOS can be achieved by using pharmacological treatments like antiandrogens, metformin, thiazolidinediones, aromatase inhibitor, and ovulation drugs to improve insulin sensitivity and ovulatory function, as well as combined oral contraceptives with or without cyproterone to resume menstrual regularity. Despite the complex pathophysiology and significant economic burden of PCOS, a comprehensive understanding of its molecular and cellular mechanisms is crucial for developing effective public health policies and treatment strategies. Nevertheless, many unknown aspects of PCOS, including detailed mechanisms of actions, along with the safety and effectiveness for the treatment, warrant further investigation.
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Affiliation(s)
- Kai-Jung Chang
- Department of Obstetrics and Gynecology, Taipei Tzu-Chi Hospital, The Buddhist Tzu-Chi Medical Foundation, New Taipei City 23142, Taiwan;
| | - Jie-Hong Chen
- Department of Medicine, MacKay Medical College, New Taipei City 25245, Taiwan;
| | - Kuo-Hu Chen
- Department of Obstetrics and Gynecology, Taipei Tzu-Chi Hospital, The Buddhist Tzu-Chi Medical Foundation, New Taipei City 23142, Taiwan;
- School of Medicine, Tzu-Chi University, Hualien 97004, Taiwan
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Siddiqui S, Mateen S, Ahmad R, Moin S. A brief insight into the etiology, genetics, and immunology of polycystic ovarian syndrome (PCOS). J Assist Reprod Genet 2022; 39:2439-2473. [PMID: 36190593 PMCID: PMC9723082 DOI: 10.1007/s10815-022-02625-7] [Citation(s) in RCA: 102] [Impact Index Per Article: 34.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2022] [Accepted: 09/19/2022] [Indexed: 10/10/2022] Open
Abstract
Polycystic ovarian syndrome (PCOS) is a prevailing endocrine and metabolic disorder occurring in about 6-20% of females in reproductive age. Most symptoms of PCOS arise early during puberty. Since PCOS involves a combination of signs and symptoms, thus it is considered as a heterogeneous disorderliness. The most accepted diagnostic criteria is Rotterdam criteria which involves two of the latter three features: (a) hyperandrogenism, (b) oligo- or an-ovulation, and (c) polycystic ovaries. The persistent hormonal imbalance leads to multiple small antral follicles formation and irregular menstrual cycle, ultimately causing infertility among females. Insulin resistance, cardiovascular diseases, abdominal obesity, psychological disorders, infertility, and cancer are also related to PCOS. These pathophysiologies associated with PCOS are interrelated with each other. Hyperandrogenism causes insulin resistance and hyperglycemia, leading to ROS formation, oxidative stress, and abdominal adiposity. In consequence, inflammation, ROS production, insulin resistance, and hyperandrogenemia also increase. Elevation of AGEs in the body either produced endogenously or consumed from diet exaggerates PCOS symptoms and is also related to ovarian dysfunction. This review summarizes how AGE formation, inflammation, and oxidative stress are significantly essential in PCOS progression. Alterations during prenatal development like exposure to excess AMH, androgens, or toxins (bisphenol-A, endocrine disruptors, etc.) may also be the etiologic mechanism behind PCOS. Although the etiology of this disorder is unclear, environmental and genetic factors are primarily involved. Physical inactivity, as well as unhealthy eating habits, has a vital role in the progression of PCOS. This review outlines a collection of specific genes phenotypically linked with PCOS. Furthermore, beneficial effect of metformin in maintaining endocrine abnormalities and ovarian function is also mentioned. Kisspeptin is a protein which helps in onset of puberty and increases GnRH pulsatile release during ovulation as well as role of KNDy neurons in GnRH pulsatile signal required for reproduction are also elaborated. This review also focuses on the immunology related to PCOS involving chronic low-grade inflammation, and how the alterations within the follicular microenvironment are intricated in the development of infertility in PCOS patients. How PCOS develops following antiepileptic and psychiatric medication is also expanded in this review. Initiation of antiandrogen treatment in early age (≤ 25 years) might be helpful in spontaneous conception in PCOS women. The role of BMP (bone morphogenetic proteins) in folliculogenesis and their expression in oocytes and granulosa cells are also explained. GDF8 and SERPINE1 expression in PCOS is given in detail.
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Affiliation(s)
- Sana Siddiqui
- Department of Biochemistry, Faculty of Medicine, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar, Pradesh -202002, India
| | - Somaiya Mateen
- Department of Biochemistry, Faculty of Medicine, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar, Pradesh -202002, India
| | - Rizwan Ahmad
- Department of Biochemistry, Faculty of Medicine, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar, Pradesh -202002, India
| | - Shagufta Moin
- Department of Biochemistry, Faculty of Medicine, Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, Uttar, Pradesh -202002, India.
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The Efficacy of Psychological Care and Chinese Herbal Decoction in Postoperative Chemotherapy Patients with Endometrial Cancer. JOURNAL OF HEALTHCARE ENGINEERING 2022; 2022:5700637. [PMID: 35222888 PMCID: PMC8881117 DOI: 10.1155/2022/5700637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/30/2021] [Revised: 01/17/2022] [Accepted: 01/21/2022] [Indexed: 11/17/2022]
Abstract
Background. In recent years, the incidence of endometrial cancer (EC) has been on the rise worldwide. The purpose of this study was to investigate the efficacy of psychological care and Chinese herbal decoction in EC patients with postoperative chemotherapy. Methods. 80 EC patients with postoperative chemotherapy were randomly divided into the observation group and control group. The control group was given psychotherapy. The observation group was given psychological care plus Chinese herbal decoction treatment. HE4, CA125, traditional Chinese medicine (TCM) syndrome scores, toxic and side effects, and quality of life scores before and after treatment were observed. Results. After treatment, the total effective rate of the observation group was higher than that of the control group. After treatment, serum HE4 and CA125 levels in the observation group were lower than those in the control group. In addition, CD3+ and CD4+ levels in the observation group were higher than those in the control group. Meanwhile, the CD8+ level in the observation group was lower than that in the control group. Compared with the control group, the quality of life in the observation group was significantly improved, and the incidence of adverse reactions was reduced. Conclusion. Chinese herbal decoction combined with psychological care can improve the clinical symptoms, alleviate the toxic and side effects, and improve the life quality of EC patients with postoperative chemotherapy.
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Hossain MA, Sharfaraz A, Hasan MI, Somadder PD, Haque MA, Sarker MR, Alam MM, Wasaf Hasan AM, Sohel M, Rahman MH. Molecular docking and pharmacology study to explore bio-active compounds and underlying mechanisms of Caesalpinia bonducella on polycystic ovarian syndrome. INFORMATICS IN MEDICINE UNLOCKED 2022. [DOI: 10.1016/j.imu.2022.101073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
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Abusailik MA, Muhanna AM, Almuhisen AA, Alhasanat AM, Alshamaseen AM, Bani Mustafa SM, Nawaiseh MB. Cutaneous manifestation of polycystic ovary syndrome. Dermatol Reports 2021; 13:8799. [PMID: 34659671 PMCID: PMC8451069 DOI: 10.4081/dr.2021.8799] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Accepted: 03/25/2021] [Indexed: 11/29/2022] Open
Abstract
The aim of this cross-sectional study, that included 146 polycystic ovary syndrome (PCOS) patients, was to evaluate the prevalence, severity and pattern of cutaneous manifestation in Jordanian women with PCOS, as well as their correlation with hormonal abnormalities. A thorough complete cutaneous examination, hormonal assays (Luteinizing hormone [LH], follicle stimulating hormone [FSH], prolactin, total testosterone, free testosterone, dehydroepiandrosterone sulfate) and pelvic ultrasonography were done. The most common cutaneous features of PCOS were acne vulgaris (75.3%) followed by hirsutism (59.6%) then seborrhea (43.2%) and androgenetic alopecia (42.5%). Patients who had acne vulgaris presented at a younger age than patients who did not. Patients who had androgenetic alopecia and stria were older than patients with no such features. Moreover, all cutaneous manifestations of PCOS, except for acne, were associated with higher body mass index (BMI). Elevated LH:FSH ratio of more than 2:1 was the most common hormonal abnormality, followed by increased LH and total testosterone. Acne, hirsutism, androgenetic alopecia, seborrhea, acanthosis nigricans and skin tags are common cutaneous manifestations among Jordanian patients with PCOS. The existence of one or more of these features, especially in overweight and obese patients, should alert the physician towards the possibility of having PCOS.
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Affiliation(s)
| | | | | | | | - Ayed M. Alshamaseen
- Department of Obstetrics and Gynecology, Jordanian Royal Medical Services, Amman
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Kaur R, Kaur T, Sudhir N, Kaur A. Association Analysis of CYP11A1 Variants with Polycystic Ovary Syndrome: a Case-Control Study from North India. Reprod Sci 2021; 28:2951-2960. [PMID: 34231171 DOI: 10.1007/s43032-021-00676-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 06/18/2021] [Indexed: 11/27/2022]
Abstract
The most common multifactorial endocrine disorder in females of reproductive age is polycystic ovary syndrome (PCOS), affecting about 5-10% of females worldwide and 9.3% of females in India. Androgen excess in PCOS is caused as a result of defects in steroidogenesis genes. CYP11A1 is an imperative marker in the steroid synthesis pathway, and the altered expression of CYP11A1 has been reported to disrupt the synthesis of steroids and hence conferring risk for the development of PCOS. The present study aimed to analyze genetic variants (rs11632698, rs4077582, rs4887139) of CYP11A1 with PCOS from North India. The study included 270 PCOS females diagnosed according to Rotterdam 2003 criteria and 270 age-matched healthy non-PCOS females. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for the genotypic analysis of the selected genetic variants. Association analysis of biochemical parameters (cholesterol, triglyceride, high-density lipoprotein) and anthropometric measurements with PCOS cases was done. The genetic variants of CYP11A1 (rs11632698, rs4077582, and rs4887139) demonstrated significant association with PCOS cases (p=1.0E-12, p=3.0E-3, p=1.0E-2, respectively). Binary logistic regression revealed that the dominant model of rs11632698 conferred 2.0 risk, and dominant as well as the co-dominant model of rs4887139 conferred risk of 2.2 and 2.4 fold, respectively, towards the progression of PCOS. The overall mean triglyceride levels were elevated, and mean HDL levels were lower in PCOS cases as compared to threshold values. The significant association of studied genetic variants suggested the important role of CYP11A1 in susceptibility to PCOS. The study was the first of its kind from our region and provided baseline data of genetics of PCOS.
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Affiliation(s)
- Ratneev Kaur
- Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, 143005, India
| | - Tajinder Kaur
- Hartej Hospital, Ranjit Avenue, Amritsar, Punjab, 143001, India
| | - Neha Sudhir
- Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, 143005, India
| | - Anupam Kaur
- Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, 143005, India.
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Miraghaee SS, Sohrabi M, Jalili C, Bahrehmand F. Assessment of GSTO1 (A140D) and GSTO2 (N142D) Gene Polymorphisms in Iranian Women with Polycystic Ovarian Syndrome. Rep Biochem Mol Biol 2020; 9:8-13. [PMID: 32821746 DOI: 10.29252/rbmb.9.1.8] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Background Glutathione S-transferases (GSTs) protect cells from oxidative stress (OS). In humans, the GST omega class contains two expressed genes, GSTO1 and GSTO2. Because OS is involved in the pathogenesis of polycystic ovary syndrome (PCOS), the aim of this study was to investigate the relationship between GSTO1 A140D (rs4925) and GSTO2 N142D (rs156697) polymorphisms in PCOS patients. Methods 175 PCOS patients and 161 healthy controls were selected among women in Kermanshah province, Iran. GSTO1 and GSTO2 were genotyped using allele-specific PCR (AS-PCR) and PCR-RFLP, respectively. Results For GSTO1, the DD genotype and the D allele led to 2.17- (P= 0.02) and 1.5-fold (P= 0.01) increases, respectively, in the odds ratios for PCOS. No significant difference was found between control and patient groups for the GSTO2 N142D genotype or allele frequency. GSTO1 and GSTO2 genotype interaction analysis showed that individuals with the GSTO1 AD or DD genotypes and the GSTO2 NN or DN genotypes had a 1.53-fold (P= 0.007) increase in PCOS risk over GSTO1 AA and GSTO2 DD individuals. Conclusion The GSTO1 A140D polymorphism is a risk factor for PCOS.
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Affiliation(s)
- Seyyed Shahram Miraghaee
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Maryam Sohrabi
- Fertility and Infertility Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Cyrus Jalili
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Fariborz Bahrehmand
- Medical Biology Research Center, Health Technology Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
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Sánchez-Ferrer ML, Prieto-Sánchez MT, Corbalán-Biyang S, Mendiola J, Adoamnei E, Hernández-Peñalver AI, Carmona-Barnosi A, Salido-Fiérrez EJ, Torres-Cantero AM. Are there differences in basal thrombophilias and C-reactive protein between women with or without PCOS? Reprod Biomed Online 2019; 38:1018-1026. [PMID: 31023609 DOI: 10.1016/j.rbmo.2019.01.013] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2018] [Revised: 01/11/2019] [Accepted: 01/24/2019] [Indexed: 02/06/2023]
Abstract
RESEARCH QUESTION Polycystic ovary syndrome (PCOS) women have increased cardiovascular risks, although it is unclear whether the haemostatic system and coagulation contribute to that increased risk. DESIGN Women attending the Gynecology Unit of the 'Virgen de la Arrixaca' University Hospital (Murcia, Spain) for routine gynaecological examinations between September 2014 and May 2016 were assessed for PCOS using the Rotterdam criteria (hyperandrogenism [H], oligo/amenorrhoea [O] and polycystic ovarian morphology [POM]) and were classified into four phenotypic. In total, 126 cases were identified and 159 control women were selected. All women underwent physical and gynaecological examinations, and blood tests between the second and fifth day of the menstrual cycle. Differences in hormonal, basal thrombophilia and metabolic parameters, and C-reactive protein (CRP) between PCOS and controls were analysed. RESULTS After adjusting by BMI and age, PCOS women had higher LH (P < 0.001), testosterone (P < 0.001), free testosterone (P = 0.01) and anti-Müllerian hormone (P < 0.001) and lower FSH (P = 0.03) compared with controls, whereas sex hormone-binding globulin was no different. Cases showed significantly higher protein S, glucose, insulin and insulin resistance (HOMA-IR) compared with controls (P < 0.05). There were no differences in protein C levels, antithrombin III, prothrombin time, homocysteine, D-dimer, factor V Leyden, prothrombin G20210A polymorphism or CRP. The H+O phenotype showed the poorest results for insulin and HOMA-IR (P = 0.04 and 0.05). CONCLUSIONS The results suggest that there are no differences in the basal thrombophilias between women with and without PCOS. However, PCOS with H+O shows the poorest metabolic profile.
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Affiliation(s)
- María L Sánchez-Ferrer
- Department of Obstetrics and Gynecology, 'Virgen de la Arrixaca' University Clinical Hospital, El Palmar Murcia 30120, Spain; Institute for Biomedical Research of Murcia, IMIB-Arrixaca, El Palmar Murcia 30120, Spain
| | - María T Prieto-Sánchez
- Department of Obstetrics and Gynecology, 'Virgen de la Arrixaca' University Clinical Hospital, El Palmar Murcia 30120, Spain; Institute for Biomedical Research of Murcia, IMIB-Arrixaca, El Palmar Murcia 30120, Spain.
| | - Shiana Corbalán-Biyang
- Department of Obstetrics and Gynecology, 'Virgen de la Arrixaca' University Clinical Hospital, El Palmar Murcia 30120, Spain
| | - Jaime Mendiola
- Institute for Biomedical Research of Murcia, IMIB-Arrixaca, El Palmar Murcia 30120, Spain; Division of Preventive Medicine and Public Health, Department of Public Health Sciences, University of Murcia School of Medicine, Espinardo Murcia 30100, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública, CIBERESP), Instituto de Salud Carlos III, Madrid 28029, Spain
| | - Evdochia Adoamnei
- Institute for Biomedical Research of Murcia, IMIB-Arrixaca, El Palmar Murcia 30120, Spain; Division of Preventive Medicine and Public Health, Department of Public Health Sciences, University of Murcia School of Medicine, Espinardo Murcia 30100, Spain
| | - Ana I Hernández-Peñalver
- Department of Obstetrics and Gynecology, 'Virgen de la Arrixaca' University Clinical Hospital, El Palmar Murcia 30120, Spain
| | - Ana Carmona-Barnosi
- Department of Obstetrics and Gynecology, 'Virgen de la Arrixaca' University Clinical Hospital, El Palmar Murcia 30120, Spain
| | - Eduardo J Salido-Fiérrez
- Institute for Biomedical Research of Murcia, IMIB-Arrixaca, El Palmar Murcia 30120, Spain; Department of Hematology and Hemotherapy, 'Virgen de la Arrixaca' University Clinical Hospital, El Palmar Murcia 30120, Spain
| | - Alberto M Torres-Cantero
- Institute for Biomedical Research of Murcia, IMIB-Arrixaca, El Palmar Murcia 30120, Spain; Division of Preventive Medicine and Public Health, Department of Public Health Sciences, University of Murcia School of Medicine, Espinardo Murcia 30100, Spain; Consortium for Biomedical Research in Epidemiology and Public Health (CIBER Epidemiología y Salud Pública, CIBERESP), Instituto de Salud Carlos III, Madrid 28029, Spain; Department of Preventive Medicine, 'Virgen de la Arrixaca' University Clinical Hospital, El Palmar Murcia 30120, Spain
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Mahran A, Abdelraheim AR, Eissa A, Gadelrab M. Does laparoscopy still has a role in modern fertility practice? Int J Reprod Biomed 2017. [DOI: 10.29252/ijrm.15.12.787] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022] Open
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Liu AL, Xie HJ, Xie HY, Liu J, Yin J, Hu JS, Peng CY. Association between fat mass and obesity associated (FTO) gene rs9939609 A/T polymorphism and polycystic ovary syndrome: a systematic review and meta-analysis. BMC MEDICAL GENETICS 2017; 18:89. [PMID: 28826396 PMCID: PMC5563909 DOI: 10.1186/s12881-017-0452-1] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/28/2016] [Accepted: 08/14/2017] [Indexed: 12/16/2022]
Abstract
Background Up to now, numerous case-control studies have reported the associations between fat mass and obesity associated (FTO) gene rs9939609 A/T polymorphism and polycystic ovary syndrome (PCOS), however, without a consistent result. Hence we performed current systematic review and meta-analysis to clarify the controversial results. Methods Case-control studies reporting the relationship of rs9939609 A/T polymorphism and PCOS published before April 2015 were searched in Pubmed database without language restriction. Data was analyzed by Review Manager 5.2. Results A total of five studies involving 5010 PCOS patients and 5300 controls were included for further meta-analysis. The results of meta-analysis showed that the FTO gene rs9939609 A/T polymorphism was significantly different between PCOS group and control group in different gene models (For AA + AT vs. TT: OR = 1.41, 95% CI = 1.28–1.55, P < 0.00001. For AA vs. AT + TT: OR = 1.54, 95% CI = 1.25–1.89, P < 0.0001. For AA vs. TT: OR = 1.74, 95% CI = 1.38–2.18, P < 0.00001. For A vs. T: OR = 1.36, 95% CI = 1.25–1.47, P < 0.00001, respectively) suggesting that A allele was a risk factor for PCOS susceptibility. Furthermore, subgroup analysis in Asian and Caucasian ethnicities also found significant association between rs9939609 A/T polymorphism and PCOS (In Asian subgroup: OR = 1.43, 95% CI = 1.29–1.59, P < 0.0001. In Caucasian subgroup: OR = 1.33, 95% CI = 1.08–1.64, P = 0.008) Conclusion This meta-analysis suggests that rs9939609 A/T polymorphism of FTO gene is associated with PCOS risk, and that A allele is a risk factor for PCOS susceptibility simultaneously.
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Affiliation(s)
- Ai Ling Liu
- Institute of Biological Science, School of Pharmaceutical and Biological Science, University of South China, Hengyang, Hunan Province, 421001, China.,Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, China.,The Key Laboratory of Biological Toxicology and Ecological Restoration of Hengyang City, Hengyang, Hunan Province, 421001, China
| | - Hui Jun Xie
- Institute of Biological Science, School of Pharmaceutical and Biological Science, University of South China, Hengyang, Hunan Province, 421001, China
| | - Hong Yan Xie
- Institute of Biological Science, School of Pharmaceutical and Biological Science, University of South China, Hengyang, Hunan Province, 421001, China
| | - Jun Liu
- Institute of Biological Science, School of Pharmaceutical and Biological Science, University of South China, Hengyang, Hunan Province, 421001, China
| | - Jie Yin
- Institute of Biological Science, School of Pharmaceutical and Biological Science, University of South China, Hengyang, Hunan Province, 421001, China
| | - Jin Song Hu
- Institute of Biological Science, School of Pharmaceutical and Biological Science, University of South China, Hengyang, Hunan Province, 421001, China
| | - Cui Ying Peng
- Institute of Biological Science, School of Pharmaceutical and Biological Science, University of South China, Hengyang, Hunan Province, 421001, China. .,Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, Hengyang, 421001, China. .,The Key Laboratory of Biological Toxicology and Ecological Restoration of Hengyang City, Hengyang, Hunan Province, 421001, China.
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Reddy BM, Kommoju UJ, Dasgupta S, Rayabarapu P. Association of type 2 diabetes mellitus genes in polycystic ovary syndrome aetiology among women from southern India. Indian J Med Res 2017; 144:400-408. [PMID: 28139539 PMCID: PMC5320846 DOI: 10.4103/0971-5916.198678] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND & OBJECTIVES Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder of premenopausal women. Given the phenotypic overlap between PCOS and type 2 diabetes mellitus (T2DM), this study was carried out to investigate whether genes implicated in T2DM were also involved in the susceptibility to PCOS among women from southern India. METHODS A total of 248 women with PCOS and 210 healthy women as controls were genotyped for a panel of 15 single nucleotide polymorphisms (SNPs) from the nine T2DM genes, such as TCF7L2, IGF2BP2, SLC30A8, HHEX, CDKAL1, CDKN2A, IRS1, CAPN10 and PPARG, on Sequenom MassARRAY platform. RESULTS None of the 15 SNPs were found to be significantly associated with PCOS after Bonferroni correction for multiple testing, either in the univariate or multivariate context. The cumulative effect of risk alleles observed with reference to T2DM was also not seen with reference to PCOS. INTERPRETATION & CONCLUSIONS The nine T2DM genes considered in this exploratory study might not be the primary susceptibility factors for PCOS among Indian women. Our results supplement the lack of evidence of the association of T2DM genes with PCOS among the Chinese and Caucasians hinting at the possible universality of this pattern. Specifically designed comprehensive studies that include women with T2DM and PCOS are required to explore the precise role of the diabetes genes.
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Affiliation(s)
- Battini Mohan Reddy
- Molecular Anthropology Group, Biological Anthropology Unit, Indian Statistical Institute, Hyderabad, India
| | - Uma Jyothi Kommoju
- Molecular Anthropology Group, Biological Anthropology Unit, Indian Statistical Institute, Hyderabad, India
| | - Shilpi Dasgupta
- Molecular Anthropology Group, Biological Anthropology Unit, Indian Statistical Institute, Hyderabad, India
| | - Pranavchand Rayabarapu
- Molecular Anthropology Group, Biological Anthropology Unit, Indian Statistical Institute, Hyderabad, India
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Jahromi MS, Tehrani FR, Hill JW, Noroozzadeh M, Zarkesh M, Ghasemi A, Zadeh-Vakili A. Alteration in follistatin gene expression detected in prenatally androgenized rats. Gynecol Endocrinol 2017; 33:433-437. [PMID: 28277126 PMCID: PMC5724370 DOI: 10.1080/09513590.2017.1290067] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
Abstract
Impaired ovarian follicle development, the hallmark of polycystic ovarian syndrome (PCOS), is believed to be due to the changes in expression of related genes such as follistatin (FST). Expression of FST gene and methylation level of its promoter in theca cells from adult female rats, prenatally exposed to androgen excess, during different phases of the estrus cycle was determined and compared with controls. Eight pregnant Wistar rats (experimental group) were treated by subcutaneous injection of 5 mg free testosterone on day 20 of pregnancy, while controls (n = 8) received 500 ml solvent. Based on observed vaginal smear, adult female offspring of mothers were divided into three groups. Levels of serum steroidogenic sexual hormones and gonadotropins, expression and promoter methylation of the FST gene were measured using ELISA, cyber-green real-time PCR and bisulfite sequence PCR (BSP), respectively. Compared to controls, the relative expression of FST gene in the treated group decreased overall by 0.85 fold; despite significant changes in different phases, but no significant differences in methylation of FST promoter. Our results reveal that manifestation of PCOS-like phenotype following prenatal exposure to excess androgen is associated with irregularity in expression of the FST gene during the estrus cycle.
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Affiliation(s)
- Marziyeh Salehi Jahromi
- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences (RIES), Shahid Beheshti University of Medical Sciences, Tehran, Iran
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences (RIES), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Fahimeh Ramezani Tehrani
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences (RIES), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Jennifer W. Hill
- Department of Physiology and Pharmacology, College of Medicine and Life Sciences, Center for Diabetes and Endocrine Research (CeDER), University of Toledo, Toledo, OH, USA and
| | - Mahsa Noroozzadeh
- Reproductive Endocrinology Research Center, Research Institute for Endocrine Sciences (RIES), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Maryam Zarkesh
- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences (RIES), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Asghar Ghasemi
- Endocrine Physiology Research Center, Research Institute for Endocrine Sciences (RIES), Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Azita Zadeh-Vakili
- Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences (RIES), Shahid Beheshti University of Medical Sciences, Tehran, Iran
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Keen MA, Shah IH, Sheikh G. Cutaneous Manifestations of Polycystic Ovary Syndrome: A Cross-Sectional Clinical Study. Indian Dermatol Online J 2017; 8:104-110. [PMID: 28405549 PMCID: PMC5372429 DOI: 10.4103/2229-5178.202275] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/24/2022] Open
Abstract
Background: Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women, affecting 5–10% of reproductive-aged women. The dermatologic manifestations of hyperandrogenism, chiefly hirsutism, acne vulgaris, androgenic alopecia, and acanthosis nigricans, are among the cardinal manifestations of PCOS. Aim: To study the incidence and prevalence of various cutaneous manifestations in patients with PCOS and to correlate these skin manifestations with hormonal changes. Settings and Design: This study was conducted at a dermatology centre over a period of 1 year from November 2012 to 2013. Materials and Methods: The present study included 100 women diagnosed to have PCOS. Hormonal analysis as well as radiological assessment was done in all the cases. Cutaneous manifestations were ascertained and inferences were drawn. Statistical Analysis: Statistical analysis was carried out by the Chi-square test and independent samples t-test. Statistical significance was determined at a level of P < 0.05. Results: In our study, the prevalence of hirsutism, acne, female pattern hair loss, acanthosis nigricans, seborrhea, striae and acrochordons was 78%, 48%, 31%, 30%, 29%, 13%, and 9%, respectively. Conclusion: Dermatologic manifestations of PCOS play a significant role in making the diagnosis and constitute a substantial portion of the symptoms experienced by women with this syndrome.
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Affiliation(s)
- Mohammad Abid Keen
- Department of Dermatology, STD and Leprosy, GMC Srinagar and associated SMHS Hospital, Srinagar, Jammu and Kashmir, India
| | - Iffat Hassan Shah
- Department of Dermatology, STD and Leprosy, GMC Srinagar and associated SMHS Hospital, Srinagar, Jammu and Kashmir, India
| | - Gousia Sheikh
- Department of Dermatology, STD and Leprosy, GMC Srinagar and associated SMHS Hospital, Srinagar, Jammu and Kashmir, India
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15
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Arora S, Sinha K, Kolte S, Mandal A. Endocrinal and autoimmune linkage: Evidences from a controlled study of subjects with polycystic ovarian syndrome. J Hum Reprod Sci 2016; 9:18-22. [PMID: 27110073 PMCID: PMC4817282 DOI: 10.4103/0974-1208.178636] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2015] [Revised: 07/10/2015] [Accepted: 01/08/2016] [Indexed: 11/24/2022] Open
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) is a metabolic syndrome, characterized by anovulation, hyperandrogenism, and polycystic ovary. With serological markers of autoimmunity found elevated in PCOS, there is a possible link between autoimmunity and PCOS. AIM The study aimed to investigate the possible correlation between autoimmune markers of autoimmune thyroiditis (AIT) and PCOS. SETTING AND DESIGN This case control study was conducted at the Department of Pathology of a tertiary care academic center during a 1-year period. MATERIALS AND METHODS Fifty-five subjects with clinical PCOS and 51 age matched control non-PCOS subjects were recruited and subjected to clinical, biochemical, and endocrinal evaluation for AIT. All subjects underwent blood glucose and serum sampling for luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, dehydroepi androsterone, thyroxine, thyroid stimulating hormone, anti-thyroid peroxidase, anti-thyroglobulin (Tg), and insulin. STATISTICAL ANALYSIS Statistical analysis was performed using SPSS version 12 for Windows. The quantitative variables are described as mean ± standard deviation. To compare quantitative variables between two groups, unpaired t-test was used. The Chi-square/Fischer's exact test was used to compare qualitative variables. ANOVA was used to compare the PCOS and non-PCOS groups. P < 0.05 was considered significant. RESULTS Significantly higher prevalence of AIT (anti-Tg antibodies) was noted in subjects with PCOS as compared to non-PCOS control subjects (P < 0.05). The PCOS subjects had higher insulin resistance index and also twice the level of LH: FSH ratio as compared to controls. CONCLUSION Higher prevalence of AIT in PCOS subjects suggest possible role of autoimmune phenomenon in the etiopathogenesis of PCOS. More data from longitudinal follow-up studies is required to clearly establish this possible link.
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Affiliation(s)
- Sheetal Arora
- Department of Pathology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
| | - Kiran Sinha
- Department of Pathology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
| | - Sachin Kolte
- Department of Pathology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
| | - Ashish Mandal
- Department of Pathology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
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Shim U, Kim HN, Lee H, Oh JY, Sung YA, Kim HL. Pathway Analysis Based on a Genome-Wide Association Study of Polycystic Ovary Syndrome. PLoS One 2015; 10:e0136609. [PMID: 26308735 PMCID: PMC4550465 DOI: 10.1371/journal.pone.0136609] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2015] [Accepted: 08/06/2015] [Indexed: 12/20/2022] Open
Abstract
Background Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in women of reproductive age, and it is affected by both environmental and genetic factors. Although the genetic component of PCOS is evident, studies aiming to identify susceptibility genes have shown controversial results. This study conducted a pathway-based analysis using a dataset obtained through a genome-wide association study (GWAS) to elucidate the biological pathways that contribute to PCOS susceptibility and the associated genes. Methods We used GWAS data on 636,797 autosomal single nucleotide polymorphisms (SNPs) from 1,221 individuals (432 PCOS patients and 789 controls) for analysis. A pathway analysis was conducted using meta-analysis gene-set enrichment of variant associations (MAGENTA). Top-ranking pathways or gene sets associated with PCOS were identified, and significant genes within the pathways were analyzed. Results The pathway analysis of the GWAS dataset identified significant pathways related to oocyte meiosis and the regulation of insulin secretion by acetylcholine and free fatty acids (all nominal gene-set enrichment analysis (GSEA) P-values < 0.05). In addition, INS, GNAQ, STXBP1, PLCB3, PLCB2, SMC3 and PLCZ1 were significant genes observed within the biological pathways (all gene P-values < 0.05). Conclusions By applying MAGENTA pathway analysis to PCOS GWAS data, we identified significant pathways and candidate genes involved in PCOS. Our findings may provide new leads for understanding the mechanisms underlying the development of PCOS.
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Affiliation(s)
- Unjin Shim
- Department of Internal Medicine, Seoul Seonam Hospital, Ewha Womans University Medical Center, Seoul, Korea
| | - Han-Na Kim
- Department of Biochemistry, Ewha Womans University School of Medicine, Seoul, Korea
| | - Hyejin Lee
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Jee-Young Oh
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
| | - Yeon-Ah Sung
- Department of Internal Medicine, Ewha Womans University School of Medicine, Seoul, Korea
- * E-mail: (YAS); (HLK)
| | - Hyung-Lae Kim
- Department of Biochemistry, Ewha Womans University School of Medicine, Seoul, Korea
- * E-mail: (YAS); (HLK)
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Gowri BV, Chandravathi PL, Sindhu PS, Naidu KS. Correlation of Skin Changes with Hormonal Changes in Polycystic Ovarian Syndrome: A Cross-sectional Study Clinical Study. Indian J Dermatol 2015; 60:419. [PMID: 26288423 PMCID: PMC4533553 DOI: 10.4103/0019-5154.160505] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
Background: Polycystic ovarian syndrome (PCOS) is a heterogenous collection of signs and symptoms that when gathered, form a spectrum of disorder with disturbance of reproductive, endocrine and metabolic functions. Aim: The aim of this study is to correlate the skin manifestations with hormonal changes and to know the incidence and prevalence of skin manifestations in patients with PCOS. Materials and Methods: A total of 40 patients with PCOS were examined during 1 year time period from May 2008 P to May 2009. Detailed clinical history was taken from each patient. PCOS was diagnosed on the basis of ultrasonography. Hormonal assays included fasting blood sugar, postprandial blood sugar, follicle-stimulating hormone, luteinizing hormone, thyroid stimulating hormone, dehydroepiandrostenedione, prolactin, free testosterone, fasting lipid profile and sex hormone binding globulin. The results obtained were statistically correlated. Results: In our study, the prevalence of cutaneous manifestations was 90%. Of all the cutaneous manifestations acne was seen in highest percentage (67.5%), followed by hirsutism (62.5%), seborrhea (52.5%), androgenetic alopecia (AGA) (30%), acanthosis nigricans (22.5%) and acrochordons (10%). Fasting insulin levels was the most common hormonal abnormality seen in both acne and hirsutism, whereas AGA was associated with high testosterone levels. Conclusion: The prevalence of cutaneous manifestations in PCOS was 90%. Hirsutism, acne, seborrhea, acanthosis nigricans and acrochordons were associated with increased levels of fasting insulin, whereas AGA showed higher levels of serum testosterone.
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Affiliation(s)
- B Vijaya Gowri
- Department of Dermatology, Care Institute of Medical Sciences, Hyderabad, Andhra Pradesh, India
| | - P L Chandravathi
- Department of Dermatology, Care Institute of Medical Sciences, Hyderabad, Andhra Pradesh, India
| | - P S Sindhu
- Department of Dermatology, Care Institute of Medical Sciences, Hyderabad, Andhra Pradesh, India
| | - K Shanthi Naidu
- Department of Lab Medicine, Care Institute of Medical Sciences, Hyderabad, Andhra Pradesh, India
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Gur EB, Karadeniz M, Turan GA. Fetal programming of polycystic ovary syndrome. World J Diabetes 2015; 6:936-42. [PMID: 26185601 PMCID: PMC4499527 DOI: 10.4239/wjd.v6.i7.936] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2014] [Revised: 02/23/2015] [Accepted: 03/30/2015] [Indexed: 02/05/2023] Open
Abstract
Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects up to 6.8% of reproductive age women. Experimental research and clinical observations suggest that PCOS may originate in the very early stages of development, possibly even during intrauterine life. This suggests that PCOS is either genetically-transmitted or is due to epigenetic alterations that develop in the intrauterine microenvironment. Although familial cases support the role of genetic factors, no specific genetic pattern has been defined in PCOS. Several candidate genes have been implicated in its pathogenesis, but none can specifically be implicated in PCOS development. Hypotheses based on the impact of the intrauterine environment on PCOS development can be grouped into two categories. The first is the "thrifty" phenotype hypothesis, which states that intrauterine nutritional restriction in fetuses causes decreased insulin secretion and, as a compensatory mechanism, insulin resistance. Additionally, an impaired nutritional environment can affect the methylation of some specific genes, which can also trigger PCOS. The second hypothesis postulates that fetal exposure to excess androgen can induce changes in differentiating tissues, causing the PCOS phenotype to develop in adult life. This review aimed to examine the role of fetal programming in development of PCOS.
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Nikokavoura EA, Johnston KL, Broom J, Wrieden WL, Rolland C. Weight loss for women with and without polycystic ovary syndrome following a very low-calorie diet in a community-based setting with trained facilitators for 12 weeks. Diabetes Metab Syndr Obes 2015; 8:495-503. [PMID: 26508882 PMCID: PMC4610794 DOI: 10.2147/dmso.s85134] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) affects between 2% and 26% of reproductive-age women in the UK, and accounts for up to 75% of anovulatory infertility. The major symptoms include ovarian disruption, hyperandrogenism, insulin resistance, and polycystic ovaries. Interestingly, at least half of the women with PCOS are obese, with the excess weight playing a pathogenic role in the development and progress of the syndrome. The first-line treatment option for overweight/obese women with PCOS is diet and lifestyle interventions; however, optimal dietary guidelines are missing. Although many different dietary approaches have been investigated, data on the effectiveness of very low-calorie diets on PCOS are very limited. MATERIALS AND METHODS The aim of this paper was to investigate how overweight/obese women with PCOS responded to LighterLife Total, a commercial very low-calorie diet, in conjunction with group behavioral change sessions when compared to women without PCOS (non-PCOS). RESULTS PCOS (n=508) and non-PCOS (n=508) participants were matched for age (age ±1 unit) and body mass index (body mass index ±1 unit). A 12-week completers analysis showed that the total weight loss did not differ significantly between PCOS (n=137) and non-PCOS participants (n=137) (-18.5±6.6 kg vs -19.4±5.7 kg, P=0.190). Similarly, the percentage of weight loss achieved by both groups was not significantly different (PCOS 17.1%±5.6% vs non-PCOS 18.2%±4.4%, P=0.08). CONCLUSION Overall, LighterLife Total could be an effective weight-loss strategy in overweight/obese women with PCOS. However, further investigations are needed to achieve a thorough way of understanding the physiology of weight loss in PCOS.
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Affiliation(s)
- Efsevia A Nikokavoura
- Centre for Obesity Research and Epidemiology, Institute for Health & Wellbeing Research (IHWR), Robert Gordon University, Aberdeen, UK
| | | | - John Broom
- Centre for Obesity Research and Epidemiology, Institute for Health & Wellbeing Research (IHWR), Robert Gordon University, Aberdeen, UK
| | - Wendy L Wrieden
- Centre for Obesity Research and Epidemiology, Institute for Health & Wellbeing Research (IHWR), Robert Gordon University, Aberdeen, UK
| | - Catherine Rolland
- Centre for Obesity Research and Epidemiology, Institute for Health & Wellbeing Research (IHWR), Robert Gordon University, Aberdeen, UK
- Correspondence: Catherine Rolland, Centre for Obesity Research and Epidemiology, Institute for Health and Wellbeing Research (IHWR), Riverside East, Robert Gordon University, Garthdee Road, Aberdeen AB10 7GJ, UK, Tel +44 1224 262 893, Fax +44 1224 262 828, Email
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20
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Ding N, Han Q, Li Q, Zhao X, Li J, Su J, Wang Q. Comprehensive analysis of Sichuan white geese (Anser cygnoides) transcriptome. Anim Sci J 2014; 85:650-9. [PMID: 24725216 DOI: 10.1111/asj.12197] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2013] [Accepted: 12/20/2013] [Indexed: 12/17/2022]
Abstract
High-throughput RNA sequencing was performed for comprehensively analyzing the transcriptome of geese. A total of 28,803,759 bp of raw sequence data was generated by 454 GS Flx+. After removal of adaptor sequences, 28,730,361 bp remained and 117,279 reads were obtained, with an average length of 244 bases. Simultaneously, complementary DNA samples from two different reproductive stages of goose ovarian, hypothalamus and pituitary tissue were sequenced separately using Illumina MiSeq platform. A total of 12 688 673 148 bp of raw sequence data were generated by Illumina MiSeq. After removal of adaptor sequences, 8 198 126 562 bp remained and 60 382 786 clean reads were obtained, with an average length of 135 bases. Assembly of all the reads from both 454 Flx+ and Illumina platforms formed 56,839 contigs. The sequence size ranges from 38 to 28,206 bp in size, with an average size of 2584 bp and an N50 of 4624. The assembly produced a substantial number of large contigs: 35,545 (62.5%) were longer than 1 kb, of which 8850 (15.6%) were longer than 5 kb. The sequencing depth was 85 X on average. We performed comprehensive function annotations on unigenes including protein sequence similarity, gene ontology (GO) term classification, and Kyoto Encylcopedia of Genes and Genomes (KEGG) pathway enrichment. GO analysis showed that approximately 63% of the contigs had annotation information, among the 35,953 annotated isotigs in Nr database, 24,783 (68.9%) sequences were assigned with one or more GO terms. There were 14,634 (40.7%) isotigs for biological processes, 10,557(29.3%) isotigs for cellular component, 22,607 (62.9%) isotigs for molecular function. The result of KEGG pathway mapping 8926 sequences had the pathway annotation, and took part in 477 pathways. Additionally, 10,685 simple sequence repeat (SSR) markers were identified from the assembled sequences. The most frequent repeat motifs were trinucleotides, which accounted for 53.03% of all SSRs, followed by dinucleotides (39.9%), tetranucleotides (5.08%), pentanucleotides (1.68%) and hexanucleotides (0.32%). Transcriptome sequencing on mixture issue of the geese yielded substantial transcriptional sequences and potentially useful SSR markers which provide an important data source for geese research.
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Affiliation(s)
- Ning Ding
- Chongqing Academy of Animal Science, Chongqing, China
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Yu M, Feng R, Sun X, Wang H, Wang H, Sang Q, Jin L, He L, Wang L. Polymorphisms of pentanucleotide repeats (tttta)n in the promoter of CYP11A1 and their relationships to polycystic ovary syndrome (PCOS) risk: a meta-analysis. Mol Biol Rep 2014; 41:4435-45. [PMID: 24610422 DOI: 10.1007/s11033-014-3314-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2013] [Accepted: 02/24/2014] [Indexed: 11/26/2022]
Abstract
Polycystic ovary syndrome (PCOS) is one of the most common endocrine diseases with an uncertain pathology and the most frequent incretory disorder in women of reproductive age, often leading to female infertility. Evidence has shown that genetic factors may contribute to the etiology of PCOS. Contradictory results have been reported concerning the association between PCOS and the CYP11A1 gene promoter -528 bp pentanucleotide (tttta)n repeat polymorphism. In order to get an overall understanding of the association between the CYP11A1 gene promoter -528 bp pentanucleotide (tttta)n repeat polymorphism and PCOS, case-control studies regarding this association were extracted from MEDLINE, Ovid EMBASE and PubMed and pooled for meta-analysis. In dichotomous allelic analyses with 1,236 PCOS patients and 1,306 control subjects, the odds ratios (ORs) were very close to 1. In dichotomous genotypic analyses with 1,063 PCOS patients and 1,176 control subjects, the (tttta)4 genotype may increase the risk of PCOS in a recessive model with OR 1.44, 95% confidence interval (CI) 1.12-1.85, and the (tttta)6 genotype may decrease the risk of PCOS in a dominant model with OR 0.76, 95% CI 0.61-0.93. In continuous analyses with 1,085 PCOS patients and 1,216 control subjects, the Mean Difference (MD) was -0.07 with a 95% CI -0.18 to 0.05, showing no difference between PCOS and control groups. No publication bias was found in either dichotomous or continuous analyses. Taken together, there may be an association between CYP11A1 promoter pentanucleotide repeat polymorphism and PCOS. Further research is needed to strictly confirm our findings.
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Affiliation(s)
- Min Yu
- Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China
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Calpain-10 genetic polymorphisms and polycystic ovary syndrome risk: A meta-analysis and meta-regression. Gene 2013; 531:426-34. [DOI: 10.1016/j.gene.2013.08.072] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2013] [Revised: 08/11/2013] [Accepted: 08/21/2013] [Indexed: 01/11/2023]
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Huang G, Coviello A. Clinical update on screening, diagnosis and management of metabolic disorders and cardiovascular risk factors associated with polycystic ovary syndrome. Curr Opin Endocrinol Diabetes Obes 2012; 19:512-9. [PMID: 23108199 DOI: 10.1097/med.0b013e32835a000e] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
PURPOSE OF REVIEW Polycystic ovarian syndrome (PCOS) is the most common endocrinopathy in premenopausal women. This review discusses the screening, diagnosis and management of metabolic disorders and cardiovascular risk factors associated with PCOS, highlighting significant recent developments. RECENT FINDINGS PCOS is a complex genetic disorder with multiple susceptibility genes as well as environmental factors influencing the expression of various PCOS phenotypes. The first genome-wide association study of PCOS identified susceptibility loci on chromosome 2 near the luteinizing hormone receptor gene LHCGR and chromosome 9 near the obesity gene DEEND1A. Women with PCOS are affected by a variety of metabolic disorders, including insulin resistance, metabolic syndrome, type-2 diabetes, dyslipidemia and obesity. Recently, it has been established that women with PCOS have a high risk of nonalcoholic fatty liver disease. These metabolic disturbances are associated with an increased risk of cardiovascular disease (CVD). Although women with PCOS have higher rates of cardiovascular risk factors and intermediate markers of CVD, studies definitively documenting increased CVD are lacking. SUMMARY The high prevalence of metabolic disorders and CVD risk factors in women with PCOS highlights the need for early screening, diagnosis and treatment of these disorders to promote long-term health and possibly prevent CVD.
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Affiliation(s)
- Grace Huang
- Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine and Boston Medical Center, Boston, Massachusetts 02118, USA
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Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev 2012; 33:981-1030. [PMID: 23065822 PMCID: PMC5393155 DOI: 10.1210/er.2011-1034] [Citation(s) in RCA: 1130] [Impact Index Per Article: 86.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Polycystic ovary syndrome (PCOS) is now recognized as an important metabolic as well as reproductive disorder conferring substantially increased risk for type 2 diabetes. Affected women have marked insulin resistance, independent of obesity. This article summarizes the state of the science since we last reviewed the field in the Endocrine Reviews in 1997. There is general agreement that obese women with PCOS are insulin resistant, but some groups of lean affected women may have normal insulin sensitivity. There is a post-binding defect in receptor signaling likely due to increased receptor and insulin receptor substrate-1 serine phosphorylation that selectively affects metabolic but not mitogenic pathways in classic insulin target tissues and in the ovary. Constitutive activation of serine kinases in the MAPK-ERK pathway may contribute to resistance to insulin's metabolic actions in skeletal muscle. Insulin functions as a co-gonadotropin through its cognate receptor to modulate ovarian steroidogenesis. Genetic disruption of insulin signaling in the brain has indicated that this pathway is important for ovulation and body weight regulation. These insights have been directly translated into a novel therapy for PCOS with insulin-sensitizing drugs. Furthermore, androgens contribute to insulin resistance in PCOS. PCOS may also have developmental origins due to androgen exposure at critical periods or to intrauterine growth restriction. PCOS is a complex genetic disease, and first-degree relatives have reproductive and metabolic phenotypes. Several PCOS genetic susceptibility loci have been mapped and replicated. Some of the same susceptibility genes contribute to disease risk in Chinese and European PCOS populations, suggesting that PCOS is an ancient trait.
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Garg P, Borel C, Sharp AJ. Detection of parent-of-origin specific expression quantitative trait loci by cis-association analysis of gene expression in trios. PLoS One 2012; 7:e41695. [PMID: 22912676 PMCID: PMC3422236 DOI: 10.1371/journal.pone.0041695] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2012] [Accepted: 06/25/2012] [Indexed: 12/02/2022] Open
Abstract
Parent-of-origin (PofO) effects, such as imprinting are a phenomenon in which homologous chromosomes exhibit differential gene expression and epigenetic modifications according to their parental origin. Such non-Mendelian inheritance patterns are generally ignored by conventional association studies, as these tests consider the maternal and paternal alleles as equivalent. To identify regulatory regions that show PofO effects on gene expression (imprinted expression Quantitative Trait Loci, ieQTLs), here we have developed a novel method in which we associate SNP genotypes of defined parental origin with gene expression levels. We applied this method to study 59 HapMap phase II parent-offspring trios. By analyzing mother/father/child trios, rules of Mendelian inheritance allowed the parental origin to be defined for ∼95% of SNPs in each child. We used 680,475 informative SNPs and corresponding expression data for 92,167 probe sets from Affymetrix GeneChip Human Exon 1.0 ST arrays and performed four independent cis-association analyses with the expression level of RefSeq genes within 1 Mb using PLINK. Independent analyses of maternal and paternal genotypes identified two significant cis-ieQTLs (p<10−7) at which expression of genes SFT2D2 and SRRT associated exclusively with maternally inherited SNPs rs3753292 and rs6945374, respectively. 28 additional suggestive cis-associations with only maternal or paternal SNPs were found at a lower stringency threshold of p<10−6, including associations with two known imprinted genes PEG10 and TRAPPC9, demonstrating the efficacy of our method. Furthermore, comparison of our method that utilizes independent analyses of maternal and paternal genotypes with the Likelihood Ratio Test (LRT) showed it to be more effective for detecting imprinting effects than the LRT. Our method represents a novel approach that can identify imprinted regulatory elements that control gene expression, suggesting novel PofO effects in the human genome.
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Affiliation(s)
- Paras Garg
- Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York, United States of America
| | - Christelle Borel
- Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York, United States of America
| | - Andrew J. Sharp
- Department of Genetics and Genomic Sciences, Mount Sinai School of Medicine, New York, New York, United States of America
- * E-mail:
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Coviello AD, Haring R, Wellons M, Vaidya D, Lehtimäki T, Keildson S, Lunetta KL, He C, Fornage M, Lagou V, Mangino M, Onland-Moret NC, Chen B, Eriksson J, Garcia M, Liu YM, Koster A, Lohman K, Lyytikäinen LP, Petersen AK, Prescott J, Stolk L, Vandenput L, Wood AR, Zhuang WV, Ruokonen A, Hartikainen AL, Pouta A, Bandinelli S, Biffar R, Brabant G, Cox DG, Chen Y, Cummings S, Ferrucci L, Gunter MJ, Hankinson SE, Martikainen H, Hofman A, Homuth G, Illig T, Jansson JO, Johnson AD, Karasik D, Karlsson M, Kettunen J, Kiel DP, Kraft P, Liu J, Ljunggren Ö, Lorentzon M, Maggio M, Markus MRP, Mellström D, Miljkovic I, Mirel D, Nelson S, Morin Papunen L, Peeters PHM, Prokopenko I, Raffel L, Reincke M, Reiner AP, Rexrode K, Rivadeneira F, Schwartz SM, Siscovick D, Soranzo N, Stöckl D, Tworoger S, Uitterlinden AG, van Gils CH, Vasan RS, Wichmann HE, Zhai G, Bhasin S, Bidlingmaier M, Chanock SJ, De Vivo I, Harris TB, Hunter DJ, Kähönen M, Liu S, Ouyang P, Spector TD, van der Schouw YT, Viikari J, Wallaschofski H, McCarthy MI, Frayling TM, Murray A, Franks S, Järvelin MR, de Jong FH, Raitakari O, Teumer A, Ohlsson C, Murabito JM, Perry JRB. A genome-wide association meta-analysis of circulating sex hormone-binding globulin reveals multiple Loci implicated in sex steroid hormone regulation. PLoS Genet 2012; 8:e1002805. [PMID: 22829776 PMCID: PMC3400553 DOI: 10.1371/journal.pgen.1002805] [Citation(s) in RCA: 126] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2012] [Accepted: 05/19/2012] [Indexed: 01/28/2023] Open
Abstract
Sex hormone-binding globulin (SHBG) is a glycoprotein responsible for the transport and biologic availability of sex steroid hormones, primarily testosterone and estradiol. SHBG has been associated with chronic diseases including type 2 diabetes (T2D) and with hormone-sensitive cancers such as breast and prostate cancer. We performed a genome-wide association study (GWAS) meta-analysis of 21,791 individuals from 10 epidemiologic studies and validated these findings in 7,046 individuals in an additional six studies. We identified twelve genomic regions (SNPs) associated with circulating SHBG concentrations. Loci near the identified SNPs included SHBG (rs12150660, 17p13.1, p = 1.8 × 10(-106)), PRMT6 (rs17496332, 1p13.3, p = 1.4 × 10(-11)), GCKR (rs780093, 2p23.3, p = 2.2 × 10(-16)), ZBTB10 (rs440837, 8q21.13, p = 3.4 × 10(-09)), JMJD1C (rs7910927, 10q21.3, p = 6.1 × 10(-35)), SLCO1B1 (rs4149056, 12p12.1, p = 1.9 × 10(-08)), NR2F2 (rs8023580, 15q26.2, p = 8.3 × 10(-12)), ZNF652 (rs2411984, 17q21.32, p = 3.5 × 10(-14)), TDGF3 (rs1573036, Xq22.3, p = 4.1 × 10(-14)), LHCGR (rs10454142, 2p16.3, p = 1.3 × 10(-07)), BAIAP2L1 (rs3779195, 7q21.3, p = 2.7 × 10(-08)), and UGT2B15 (rs293428, 4q13.2, p = 5.5 × 10(-06)). These genes encompass multiple biologic pathways, including hepatic function, lipid metabolism, carbohydrate metabolism and T2D, androgen and estrogen receptor function, epigenetic effects, and the biology of sex steroid hormone-responsive cancers including breast and prostate cancer. We found evidence of sex-differentiated genetic influences on SHBG. In a sex-specific GWAS, the loci 4q13.2-UGT2B15 was significant in men only (men p = 2.5 × 10(-08), women p = 0.66, heterogeneity p = 0.003). Additionally, three loci showed strong sex-differentiated effects: 17p13.1-SHBG and Xq22.3-TDGF3 were stronger in men, whereas 8q21.12-ZBTB10 was stronger in women. Conditional analyses identified additional signals at the SHBG gene that together almost double the proportion of variance explained at the locus. Using an independent study of 1,129 individuals, all SNPs identified in the overall or sex-differentiated or conditional analyses explained ~15.6% and ~8.4% of the genetic variation of SHBG concentrations in men and women, respectively. The evidence for sex-differentiated effects and allelic heterogeneity highlight the importance of considering these features when estimating complex trait variance.
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Affiliation(s)
- Andrea D. Coviello
- Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Massachusetts, United States of America
- Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine, Boston, Massachusetts, United States of America
- National Heart, Lung, and Blood Institute's The Framingham Heart Study, Framingham, Massachusetts, United States of America
| | - Robin Haring
- Institute for Clinical Chemistry and Laboratory Medicine, University Medicine, Ernst-Moritz-Arndt University of Greifswald, Greifswald, Germany
| | - Melissa Wellons
- Department of Medicine and Department of Obstetrics and Gynecology, The University of Alabama at Birmingham, Birmingham, Alabama, United States of America
| | - Dhananjay Vaidya
- Department of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America
| | - Terho Lehtimäki
- Department of Clinical Chemistry, Fimlab Laboratories, Tampere University Hospital and University of Tampere School of Medicine, Tampere, Finland
| | - Sarah Keildson
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
| | - Kathryn L. Lunetta
- Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America
| | - Chunyan He
- Department of Public Health, Indiana University School of Medicine, Indianapolis, Indiana, United States of America
- Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, Indiana, United States of America
| | - Myriam Fornage
- University of Texas Health Sciences Center at Houston, Houston, Texas, United States of America
| | - Vasiliki Lagou
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
- Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Oxford, United Kingdom
| | - Massimo Mangino
- Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
| | - N. Charlotte Onland-Moret
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Brian Chen
- Program on Genomics and Nutrition and the Center for Metabolic Disease Prevention, School of Public Health, University of California Los Angeles, Los Angeles, California, United States of America
| | - Joel Eriksson
- Center for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Melissa Garcia
- Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, Maryland, United States of America
| | - Yong Mei Liu
- Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America
- Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest University Health Sciences, Winston-Salem, North Carolina, United States of America
| | - Annemarie Koster
- Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, Maryland, United States of America
| | - Kurt Lohman
- Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States of America
| | - Leo-Pekka Lyytikäinen
- Department of Clinical Chemistry, Fimlab Laboratories, Tampere University Hospital and University of Tampere School of Medicine, Tampere, Finland
| | - Ann-Kristin Petersen
- Institute of Genetic Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany
| | - Jennifer Prescott
- Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America
- Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, United States of America
| | - Lisette Stolk
- Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands
- Netherlands Consortium of Healthy Aging, Rotterdam, The Netherlands
| | - Liesbeth Vandenput
- Center for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Andrew R. Wood
- Genetics of Complex Traits, Peninsula Medical School, University of Exeter, Exeter, United Kingdom
| | - Wei Vivian Zhuang
- Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America
| | - Aimo Ruokonen
- Institute of Diagnostics, University of Oulu, Oulu, Finland
| | | | - Anneli Pouta
- National Institute for Health and Welfare and Institute of Health Sciences, University of Oulu, Oulu, Finland
| | | | - Reiner Biffar
- Department of Prosthetic Dentistry, Gerostomatology, and Dental Materials, University of Greifswald, Greifswald, Germany
| | - Georg Brabant
- Experimental and Clinical Endocrinology, University of Lübeck, Lübeck, Germany
| | - David G. Cox
- Cancer Research Center of Lyon, INSERM U1052, Lyon, France
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom
| | - Yuhui Chen
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
| | - Steven Cummings
- California Pacific Medical Center, San Francisco, California, United States of America
| | - Luigi Ferrucci
- Longitudinal Studies Section, Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, United States of America
| | - Marc J. Gunter
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College, London, United Kingdom
| | - Susan E. Hankinson
- Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, United States of America
- Division of Biostatistics and Epidemiology, University of Massachusetts, Amherst, Massachusetts, United States of America
- Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America
| | - Hannu Martikainen
- Department of Obstetrics and Gynecology, University Hospital of Oulu, Oulu, Finland
| | - Albert Hofman
- Netherlands Consortium of Healthy Aging, Rotterdam, The Netherlands
- Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands
| | - Georg Homuth
- Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany
| | - Thomas Illig
- Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, Neuherberg, Germany
- Hannover Unified Biobank, Hannover Medical School, Hannover, Germany
| | - John-Olov Jansson
- Center for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Andrew D. Johnson
- National Heart, Lung, and Blood Institute's The Framingham Heart Study, Framingham, Massachusetts, United States of America
| | - David Karasik
- Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, Massachusetts, United States of America
| | - Magnus Karlsson
- Clinical and Molecular Osteoporosis Research Unit, Department of Clinical Sciences and Department of Orthopaedics, Lund University, Malmö, Sweden
| | - Johannes Kettunen
- Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
- Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
| | - Douglas P. Kiel
- Hebrew SeniorLife Institute for Aging Research and Harvard Medical School, Boston, Massachusetts, United States of America
| | - Peter Kraft
- Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America
| | - Jingmin Liu
- Women's Health Initiative Clinical Coordinating Center, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
| | - Östen Ljunggren
- Department of Medical Sciences, University of Uppsala, Uppsala, Sweden
| | - Mattias Lorentzon
- Center for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Marcello Maggio
- Department of Internal Medicine and Biomedical Sciences, Section of Geriatrics, University of Parma, Parma, Italy
| | | | - Dan Mellström
- Center for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Iva Miljkovic
- University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
| | - Daniel Mirel
- Gene Environment Initiative, Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Boston, Massachusetts, United States of America
| | - Sarah Nelson
- Department of Biostatistics, University of Washington, Seattle, Washington, United States of America
| | - Laure Morin Papunen
- Department of Obstetrics and Gynecology, University Hospital of Oulu, Oulu, Finland
| | - Petra H. M. Peeters
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Inga Prokopenko
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
- Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Oxford, United Kingdom
| | - Leslie Raffel
- Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America
| | - Martin Reincke
- Medizinische Klinik and Poliklinik IV, Ludwig-Maximilians University, Munich, Germany
| | - Alex P. Reiner
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America
| | - Kathryn Rexrode
- Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America
| | - Fernando Rivadeneira
- Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands
- Netherlands Consortium of Healthy Aging, Rotterdam, The Netherlands
| | - Stephen M. Schwartz
- Cardiovascular Health Research Unit, Department of Epidemiology, University of Washington, Seattle, Washington, United States of America
| | - David Siscovick
- Cardiovascular Health Research Unit, Department of Epidemiology, University of Washington, Seattle, Washington, United States of America
| | - Nicole Soranzo
- Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
- Human Genetics, Wellcome Trust Sanger Institute, Hinxton, United Kingdom
| | - Doris Stöckl
- Institute of Epidemiology II, Helmholtz Zentrum München, Neuherberg, Germany
- Department of Obstetrics and Gynaecology, Ludwig-Maximilians-University, Munich, Germany
| | - Shelley Tworoger
- Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, United States of America
- Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America
| | - André G. Uitterlinden
- Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands
- Netherlands Consortium of Healthy Aging, Rotterdam, The Netherlands
- Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands
| | - Carla H. van Gils
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Ramachandran S. Vasan
- Section of Preventive Medicine and Epidemiology, Boston University School of Medicine, Boston, Massachusetts, United States of America
- National Heart, Lung, and Blood Institute's The Framingham Heart Study, Framingham, Massachusetts, United States of America
| | - H.-Erich Wichmann
- Institute of Epidemiology I, Helmholtz Zentrum München, Neuherberg, Germany
- Institute of Medical Informatics, Biometry, and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany
- Klinikum Großhadern, Munich, Germany
| | - Guangju Zhai
- Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
- Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada
| | - Shalender Bhasin
- Section of Endocrinology, Diabetes, and Nutrition, Boston University School of Medicine, Boston, Massachusetts, United States of America
| | - Martin Bidlingmaier
- Medizinische Klinik and Poliklinik IV, Ludwig-Maximilians University, Munich, Germany
| | - Stephen J. Chanock
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America
| | - Immaculata De Vivo
- Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America
- Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, United States of America
| | - Tamara B. Harris
- Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, Maryland, United States of America
| | - David J. Hunter
- Program in Molecular and Genetic Epidemiology, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America
- Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School, Boston, Massachusetts, United States of America
| | - Mika Kähönen
- Department of Clinical Physiology, Tampere University Hospital and University of Tampere School of Medicine, Tampere, Finland
| | - Simin Liu
- Program on Genomics and Nutrition, Department of Epidemiology, University of California Los Angeles, Los Angeles, California, United States of America
| | - Pamela Ouyang
- Division of Cardiology, Johns Hopkins Bayview Medical Center, Baltimore, Maryland, United States of America
| | - Tim D. Spector
- Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
| | - Yvonne T. van der Schouw
- Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Jorma Viikari
- Department of Medicine, Turku University Hospital and University of Turku, Turku, Finland
| | - Henri Wallaschofski
- Institute for Clinical Chemistry and Laboratory Medicine, University Medicine, Ernst-Moritz-Arndt University of Greifswald, Greifswald, Germany
| | - Mark I. McCarthy
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
- Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Churchill Hospital, Oxford, United Kingdom
- Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, United Kingdom
| | - Timothy M. Frayling
- Genetics of Complex Traits, Peninsula Medical School, University of Exeter, Exeter, United Kingdom
| | - Anna Murray
- Genetics of Complex Traits, Peninsula Medical School, University of Exeter, Exeter, United Kingdom
| | - Steve Franks
- Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom
| | - Marjo-Riitta Järvelin
- Department of Biostatistics and Epidemiology, School of Public Health, MRC-HPA Centre for Environment and Health, Faculty of Medicine, Imperial College London, London, United Kingdom
- Institute of Health Sciences, University of Oulu, Oulu, Finland
- Biocenter Oulu, University of Oulu, Oulu, Finland
- National Institute of Health and Welfare, University of Oulu, Oulu, Finland
| | - Frank H. de Jong
- Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands
| | - Olli Raitakari
- Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital and Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
| | - Alexander Teumer
- Interfaculty Institute for Genetics and Functional Genomics, University of Greifswald, Greifswald, Germany
| | - Claes Ohlsson
- Center for Bone and Arthritis Research, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Joanne M. Murabito
- National Heart, Lung, and Blood Institute's The Framingham Heart Study, Framingham, Massachusetts, United States of America
- Section of General Internal Medicine, Boston University School of Medicine, Boston, Massachusetts, United States of America
| | - John R. B. Perry
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom
- Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom
- Genetics of Complex Traits, Peninsula Medical School, University of Exeter, Exeter, United Kingdom
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Capalbo A, Sagnella F, Apa R, Fulghesu AM, Lanzone A, Morciano A, Farcomeni A, Gangale MF, Moro F, Martinez D, Ciardulli A, Palla C, Uras ML, Spettu F, Cappai A, Carcassi C, Neri G, Tiziano FD. The 312N variant of the luteinizing hormone/choriogonadotropin receptor gene (LHCGR) confers up to 2·7-fold increased risk of polycystic ovary syndrome in a Sardinian population. Clin Endocrinol (Oxf) 2012; 77:113-9. [PMID: 22356187 DOI: 10.1111/j.1365-2265.2012.04372.x] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
OBJECTIVE Polycystic ovary syndrome (PCOS) is a frequent condition, affecting about 15% of women of reproductive age. Because of its familial occurrence, a multifactorial model of susceptibility, including both genetic and environmental factors, has been proposed. However, the identification of genetic factors has been elusive. DESIGN Case-control study aimed at evaluating possible associations between functionally relevant variants of the luteinizing hormone/choriogonadotrophin receptor gene (LHCGR) and PCOS phenotype. PATIENTS A total of 198 PCOS and 187 non-PCOS women, aged 14-35 years, of Sardinian origin, were referred to the outpatient clinic of the Department of Obstetrics and Gynaecology of the University of Cagliari (Sardinia). PCOS diagnosis was based on the Rotterdam criteria. MEASUREMENTS We determined the genotype of ins18LQ, S291N and S312N variants at the LHCGR locus. Genotype was related to the presence or absence of PCOS and to several clinical and biochemical characteristics. RESULTS The presence of at least one 312N allele was strongly associated with PCOS risk (OR, 2·04; 95% CI, 1·32-3·14; χ(2) , 10·47; P = 0·001). 312N homozygosity was associated with a further risk increase (OR, 2·73; 95% CI, 1·25-5·95; χ(2) , 6·65; P = 0·01). The number of ins18LQ alleles was associated with LH serum levels in controls (χ(2) , 8·04, P = 0·017). CONCLUSIONS For the first time, we have identified a genetic variant that is strongly associated with PCOS in an isolated population. These results, if confirmed in other cohorts, may provide the opportunity to test the S312N genotype at the LHCGR locus in fertile women to assess the risk of PCOS. The avoidance of triggering factors like weight increase may improve the reproductive outcome of potentially at-risk subjects.
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Affiliation(s)
- A Capalbo
- Istituto di Genetica Medica, Università Cattolica del Sacro Cuore, Roma, Italy
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Tang ST, Wang CJ, Tang HQ, Peng WJ, Wang YM, Zhang Q. Association of Pro12Ala polymorphism in peroxisome proliferator-activated receptor gamma with polycystic ovary syndrome: a meta-analysis. Mol Biol Rep 2012; 39:9649-60. [DOI: 10.1007/s11033-012-1830-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2012] [Accepted: 06/10/2012] [Indexed: 10/28/2022]
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29
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Schweighofer N, Lerchbaum E, Trummer O, Schwetz V, Pilz S, Pieber TR, Obermayer-Pietsch B. Androgen levels and metabolic parameters are associated with a genetic variant of F13A1 in women with polycystic ovary syndrome. Gene 2012; 504:133-9. [PMID: 22565190 DOI: 10.1016/j.gene.2012.04.050] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2011] [Revised: 03/08/2012] [Accepted: 04/18/2012] [Indexed: 12/31/2022]
Abstract
The polycystic ovary syndrome (PCOS), characterized by hyperandrogenism, is one of the most common hormonal disorders among premenopausal women and is associated with infertility, obesity, and insulin resistance. Accumulating evidence suggests a role of the blood coagulation factor gene F13A1 in obesity (GeneBank ID: NM_000129.3). The aim of this study was to investigate the association of intronic allelic variants of the F13A1 gene with PCOS susceptibility and metabolic parameters in lean and obese PCOS women. In a case-control study, we determined an intronic F13A1 single nucleotide polymorphism (SNP) (dbSNP ID: rs7766109) in 585 PCOS and 171 control women and tested for PCOS susceptibility and associations with anthropometric, metabolic and hormonal parameters. Genotype frequencies of the F13A1 SNP rs7766109 were equivalent in PCOS and control women. In PCOS women, F13A1 gene variants were significantly associated with body mass index (BMI) (p=0.013), systolic blood pressure (p=0.042), insulin response (AUCins) (p=0.015), triglycerides (TG) (p=0.001), and high density lipoprotein cholesterol (HDL) (p=0.012). In the subgroup of obese PCOS women free androgen index (FAI), free testosterone and sex hormone binding globulin (SHBG) as well as glucose measurements showed a significantly different pattern across F13A1 gene variants (p=0.043; p=0.039 and p=0.013, respectively). We report for the first time an association of the F13A1 SNP rs7766109 with BMI, androgens, and insulin resistance in PCOS women. Further studies are needed to confirm our findings and to evaluate whether F13A1 is causally involved in the pathogenesis of PCOS related metabolic and hormonal disturbances.
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Affiliation(s)
- N Schweighofer
- Medical University of Graz, Division of Endocrinology and Metabolism, Department of Internal Medicine, Auenbruggerplatz 15, 8036 Graz, Austria
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30
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Dasgupta S, Sirisha PVS, Neelaveni K, Anuradha K, Reddy BM. Association of CAPN10 SNPs and haplotypes with polycystic ovary syndrome among South Indian Women. PLoS One 2012; 7:e32192. [PMID: 22384174 PMCID: PMC3285666 DOI: 10.1371/journal.pone.0032192] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2011] [Accepted: 01/24/2012] [Indexed: 11/25/2022] Open
Abstract
Polycystic Ovary Syndrome (PCOS) is known to be characterized by metabolic disorder in which hyperinsulinemia and peripheral insulin resistance are central features. Given the physiological overlap between PCOS and type-2 diabetes (T2DM), and calpain 10 gene (CAPN10) being a strong candidate for T2DM, a number of studies have analyzed CAPN10 SNPs among PCOS women yielding contradictory results. Our study is first of its kind to investigate the association pattern of CAPN10 polymorphisms (UCSNP-44, 43, 56, 19 and 63) with PCOS among Indian women. 250 PCOS cases and 299 controls from Southern India were recruited for this study. Allele and genotype frequencies of the SNPs were determined and compared between the cases and controls. Results show significant association of UCSNP-44 genotype CC with PCOS (p = 0.007) with highly significant odds ratio when compared to TC (OR = 2.51, p = 0.003, 95% CI = 1.37–4.61) as well as TT (OR = 1.94, p = 0.016, 95% CI = 1.13–3.34). While the haplotype carrying the SNP-44 and SNP-19 variants (21121) exhibited a 2 fold increase in the risk for PCOS (OR = 2.37, p = 0.03), the haplotype containing SNP-56 and SNP-19 variants (11221) seems to have a protective role against PCOS (OR = 0.20, p = 0.004). Our results support the earlier evidence for a possible role of UCSNP-44 of the CAPN10 gene in the manifestation of PCOS.
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Affiliation(s)
- Shilpi Dasgupta
- Molecular Anthropology Group, Biological Anthropology Unit, Indian Statistical Institute, Hyderabad, Andhra Pradesh, India
| | - Pisapati V. S. Sirisha
- Molecular Anthropology Group, Biological Anthropology Unit, Indian Statistical Institute, Hyderabad, Andhra Pradesh, India
| | - Kudugunti Neelaveni
- Department of Endocrinology, Osmania General Hospital, Hyderabad, Andhra Pradesh, India
| | | | - B. Mohan Reddy
- Molecular Anthropology Group, Biological Anthropology Unit, Indian Statistical Institute, Hyderabad, Andhra Pradesh, India
- * E-mail:
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Zhao H, Xu X, Xing X, Wang J, He L, Shi Y, Shi Y, Zhao Y, Chen ZJ. Family-based analysis of susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3. Hum Reprod 2011; 27:294-8. [PMID: 22081247 DOI: 10.1093/humrep/der379] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Polycystic ovary syndrome (PCOS) is a complex endocrine-metabolic disorder. A previous genome-wide association study (GWAS) identified five single nucleotide polymorphisms (SNPs) which were independently associated with PCOS in Han Chinese. To overcome population stratification, a family-based analysis was conducted to validate whether these five SNPs are associated with PCOS. METHODS A total of 276 family trios (828 participants) having a proband with PCOS were included in the family-based study. The transmission disequilibrium test (TDT) was used to analyze the association between PCOS and five SNPs rs13429458, rs12478601, rs13405728, rs10818854 and rs2479106 in three susceptible loci 2p16.3, 2p21 and 9q33.3. RESULTS A positive association was observed for the SNP rs13429458 (P= 3.74 × 10(-5)). CONCLUSIONS TDT confirms that SNP rs13429458, in the THADA gene, is significantly associated with risk of PCOS. This family-based analysis enhances our previous case-control GWAS and provides further support for the role of susceptibility loci in PCOS.
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Affiliation(s)
- Han Zhao
- Center for Reproductive Medicine, Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, 250021 Jinan, People's Republic of China
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Calogero AE, Calabrò V, Catanuso M, Condorelli RA, La Vignera S. Understanding polycystic ovarian syndrome pathogenesis: an updated of its genetic aspects. J Endocrinol Invest 2011; 34:630-44. [PMID: 21606667 DOI: 10.3275/7746] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Polycystic ovary syndrome (PCOS) is the most frequent cause of female infertility. It is also characterized by metabolic defects that raise the risk for cardiovascular disease. Despite the progress in the definition of the clinical aspects of the syndrome, only very few definite data are available about the ethiopathogenetic mechanisms that subtend PCOS. It is likely that the PCOS phenotype derives from the interaction between environmental and genetic factors. While environmental factors have easily been investigated, the individuation of the genetic factors seem to be more complex. Indeed, PCOS appears to be inherited as a complex, polygenic trait. Several family studies have been conducted with the aim to clarify the genetic aspects of PCOS, but their findings are often conflicting and not conclusive.Moreover, it is difficult to establish with certainty which genes are involved and their effective role in the development of the syndrome because in PCOS, genetic analysis is hampered by low fecundity, lack of a male phenotype, absence of an animal model, and dissimilarity of the diagnostic criteria used to select the patients. Since multiple biochemical pathways are implicated in PCOS pathogenesis, genes of steroid hormone metabolism, gonadotropin release and action, insulin secretion and action, adipose tissue metabolism and others have been investigated. Nevertheless, none of them seems to play a key role in the ethiopathogenesis of PCOS. This article reviews the large body of literature generated to support the presence of genetic abnormalities in PCOS women by taking in consideration the most important studies regarding PCOS candidate genes.
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Affiliation(s)
- A E Calogero
- Section of Endocrinology, Andrology and Internal Medicine, Department of Internal Medicine and Systemic Diseases, and Master in Andrological, Human Reproduction and Biotechnology Sciences, University of Catania, Catania, Italy.
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Unluturk U, Harmanci A, Kocaefe C, Yildiz BO. The Genetic Basis of the Polycystic Ovary Syndrome: A Literature Review Including Discussion of PPAR-gamma. PPAR Res 2011; 2007:49109. [PMID: 17389770 PMCID: PMC1820621 DOI: 10.1155/2007/49109] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2006] [Revised: 11/24/2006] [Accepted: 12/03/2006] [Indexed: 02/06/2023] Open
Abstract
Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of the women of reproductive age. Familial clustering of PCOS has been consistently reported suggesting that genetic factors play a role in the development of the syndrome although PCOS cases do not exhibit a clear pattern of Mendelian inheritance. It is now well established that PCOS represents a complex trait similar to type-2 diabetes and obesity, and that both inherited and environmental factors contribute to the PCOS pathogenesis. A large number of functional candidate genes have been tested for association or linkage with PCOS phenotypes with more negative than positive findings. Lack of universally accepted diagnostic criteria, difficulties in the assignment of male phenotype, obscurity in the mode of inheritance, and particularly small sample size of the study populations appear to be major limitations for the genetic studies of PCOS. In the near future, utilizing the genome-wide scan approach and the HapMap project will provide a stronger potential for the genetic analysis of the syndrome.
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Affiliation(s)
- Ugur Unluturk
- Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Hacettepe, 06100 Ankara, Turkey
| | - Ayla Harmanci
- Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Hacettepe, 06100 Ankara, Turkey
- Endocrinology and Metabolism Unit, Faculty of Medicine, Hacettepe University, Hacettepe, 06100 Ankara, Turkey
| | - Cetin Kocaefe
- Department of Medical Biology, Faculty of Medicine, Hacettepe University, Hacettepe, 06100 Ankara, Turkey
| | - Bulent O. Yildiz
- Department of Internal Medicine, Faculty of Medicine, Hacettepe University, Hacettepe, 06100 Ankara, Turkey
- Endocrinology and Metabolism Unit, Faculty of Medicine, Hacettepe University, Hacettepe, 06100 Ankara, Turkey
- *Bulent O. Yildiz:
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Sloboda DM, Hickey M, Hart R. Reproduction in females: the role of the early life environment. Hum Reprod Update 2010; 17:210-27. [DOI: 10.1093/humupd/dmq048] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023] Open
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Tso L. The use of metformin in assisted reproductive techniques for polycystic ovary syndrome patients. MIDDLE EAST FERTILITY SOCIETY JOURNAL 2010. [DOI: 10.1016/j.mefs.2010.09.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
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Ganie MA, Marwaha RK, Aggarwal R, Singh S. High prevalence of polycystic ovary syndrome characteristics in girls with euthyroid chronic lymphocytic thyroiditis: a case-control study. Eur J Endocrinol 2010; 162:1117-22. [PMID: 20332127 DOI: 10.1530/eje-09-1012] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE The aim was to find the prevalence of polycystic ovary syndrome (PCOS) phenotype in adolescent euthyroid girls with chronic lymphocytic thyroiditis (CLT). DESIGN This was a prospective case-control study as part of an ongoing community-wide thyroid survey in Indian schools. METHODS One hundred and seventy-five girls with euthyroid CLT and 46 age-matched non-CLT girls underwent clinical, biochemical, hormonal, and ultrasonographic evaluation for diagnosis of PCOS by Rotterdam 2003 criteria. All subjects underwent serum sampling for LH, FSH, testosterone, DHEAS, free thyroxine, TSH, and anti-thyroid peroxidase (TPO) antibodies. Oral glucose tolerance test (OGTT) was undertaken for plasma glucose and insulin. RESULTS Significantly higher prevalence of PCOS was noted in girls with euthyroid CLT when compared to their control counterparts (46.8 vs 4.3%, P=0.001). The CLT girls had higher body mass index, waist circumference, and systolic blood pressure (P=0.001). Mean number of menstrual cycles/year was 8.4+/-3.5 vs 10.1+/-1.4, and mean Ferriman-Gallwey score was 11.9+/-3.5 vs 3.0+/-2.4 (P=0.001) in cases versus controls respectively. The fasting and postprandial glucose and serum cholesterol were also higher in the cases (P=0.001). Homeostasis model assessment-insulin resistance was 4.4+/-4.2 vs 2.3+/-2.7 in the cases versus controls (P=0.001). CONCLUSION Higher prevalence of PCOS characteristics in euthyroid CLT girls when compared to controls suggest possible role of autoimmune phenomenon in the etiopathogenesis of PCOS. Further studies are required to understand the pathogenic link between these two disorders.
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Affiliation(s)
- Mohd Ashraf Ganie
- Department of Endocrinology and Thyroid Research Centre, Institute of Nuclear Medicine and Allied Sciences, Lucknow Road, Timarpur, New Delhi, India
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Demirci H, Yilmaz M, Ergun MA, Yurtcu E, Bukan N, Ayvaz G. Frequency of adiponectin gene polymorphisms in polycystic ovary syndrome and the association with serum adiponectin, androgen levels, insulin resistance and clinical parameters. Gynecol Endocrinol 2010; 26:348-55. [PMID: 20388053 DOI: 10.3109/09513590903367051] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023] Open
Abstract
AIM Although the association between adiponectin gene polymorphisms and insulin resistance has been investigated in many studies, there are only a few studies, which have investigated adiponectin gene polymorphisms in patients with polycystic ovary syndrome (PCOS). The objectives of this study were to determine the frequency of T45G polymorphisms localised in exon 2 of the adiponectin gene in a Turkish population with PCOS and to determine the association of T45G polymorphisms with insulin resistance and serum adiponectin levels in PCOS. MATERIALS AND METHODS Ninety-six patients with PCOS and 93 healthy control subjects were included in the study. Insulin resistance was estimated via HOMA-IR. Serum adiponectin levels were measured by ELISA. For determination of adiponectin gene polymorphisms, PCR was performed with appropriate primers after genomic DNA was obtained from the peripheral blood of the patients and control subjects. RESULTS Adiponectin levels were low in patients with PCOS than control subjects. There was no significant statistical difference between the PCOS and control groups with respect to the frequency of polymorphisms and the genotype distribution. Adiponectin gene polymorphisms were not associated with the anthropometric parameters, hyperandrogenism and adiponectin levels in PCOS. However, the fasting insulin level and insulin resistance were significantly higher and more frequent, respectively, in the polymorphic group compared to the other genotypes among patients with PCOS. CONCLUSION The risk of PCOS, hyperandrogenism in patients with PCOS and low serum adiponectin levels cannot be directly attributed to T45G adiponectin gene polymorphisms in exon 2, rather these polymorphisms may be associated with insulin resistance and hyperinsulinemia in PCOS.
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Affiliation(s)
- Hüseyin Demirci
- Balikesir Ataturk Government Hospital, Department of Endocrinology, Balikesir, Turkey
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38
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Jiang B, Kenna HA, Rasgon NL. Genetic overlap between polycystic ovary syndrome and bipolar disorder: The endophenotype hypothesis. Med Hypotheses 2009; 73:996-1004. [DOI: 10.1016/j.mehy.2008.12.056] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2008] [Revised: 12/03/2008] [Accepted: 12/07/2008] [Indexed: 12/13/2022]
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Zhuo G, Feng G, Leng J, Yu L, Jiang Y. A 9-bp deletion homoplasmy in women with polycystic ovary syndrome revealed by mitochondrial genome-mutation screen. Biochem Genet 2009; 48:157-63. [PMID: 20094848 DOI: 10.1007/s10528-009-9308-5] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2008] [Accepted: 11/02/2009] [Indexed: 10/20/2022]
Abstract
Polycystic ovary syndrome (PCOS) is a complex and heterogeneous disorder presenting a challenge for clinical investigators. To investigate the association of a mitochondrial genetic basis with PCOS, we screened mutations of the whole mitochondrial genome in 57 women patients with PCOS and 38 healthy control individuals. Two-step PCR reactions were adopted to amplify and sequence the whole mitochondrial genome. A 9-bp deletion variant appeared in homoplasmy between PCOS patients and control individuals. In the 62 individuals with complete sequences, eight of 34 (23.5%) patients showed the 9-bp deletion, compared with only two of 28 (7.1%) in healthy controls. The 9-bp deletion variant in region V of mitochondrial DNA may be associated with the heterogeneous disorder PCOS.
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Affiliation(s)
- Guangchao Zhuo
- Center of Clinical Experimental Medicine, First People's Hospital of Hangzhou, Hangzhou, China.
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40
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Abstract
The polycystic ovary syndrome is the most common endocrine disorder affecting women. It is a heterogeneous familial condition of uncertain aetiology. The diagnosis is made by the detection of polycystic ovaries on ultrasound examination and the occurrence of single or multiple clinical features such as menstrual cycle disturbances, obesity, acne, hirsutism, alopecia and biochemical abnormalities such as hypersecretion of luteinising hormone and testosterone. In a significant number of women with this condition there is impaired insulin metabolism. Women with the polycystic ovary syndrome are at an increased risk of developing diabetes and possibly cardiovascular disease in later life. The management should be symptom-orientated. Menstrual cycle regulation may be attained with the combined oral contraceptive pill or cyclical progestogen therapy. In obese women, with the loss of weight, the symptoms and endocrine profile are generally improved. Short-term treatment with metformin may be useful in women with insulin resistance. Hyperandrogenism may be treated with the contraceptive pill containing cyproterone acetate or with short-term low-dose anti-androgen therapy, together with effective contraception. Ovulation may be induced with clomiphene citrate with careful monitoring, failing which low-dose gonadotrophin therapy or laparoscopic ovarian diathermy are effective options.
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Affiliation(s)
- R K Bhathena
- Department of Obstetrics and Gynaecology, Petit Parsee General and Masina Hospitals, 40 Cuffe Parade, Bombay 5, India.
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Kim JJ, Choi YM, Choung SH, Yoon SH, Lee GH, Moon SY. Estrogen receptor beta gene +1730 G/A polymorphism in women with polycystic ovary syndrome. Fertil Steril 2009; 93:1942-7. [PMID: 19185861 DOI: 10.1016/j.fertnstert.2008.12.040] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2008] [Revised: 11/11/2008] [Accepted: 12/10/2008] [Indexed: 11/16/2022]
Abstract
OBJECTIVE To investigate whether the +1730 G/A polymorphism in the estrogen receptor (ER)-beta gene is associated with susceptibility to polycystic ovary syndrome (PCOS). DESIGN Case-control study. SETTING University Department of Obstetrics and Gynecology. PATIENT(S) Women with (n = 138) or without (n = 290) PCOS. INTERVENTION(S) Genotyping was performed by polymerase chain reaction-restriction fragment-length polymorphism analysis. MAIN OUTCOME MEASURE(S) Genotype distribution and allele frequency of the +1730 G/A polymorphism in the ER-beta gene. RESULT(S) There was a significant difference in the genotype distribution between the patients with PCOS and controls (non-GG rates were 22.1% for patients with PCOS and 36.6% for controls). There was also a significant difference in the G and A allele frequencies between these two groups (11.7% in patients vs. 19.1% in controls with A allele). But in patients with PCOS there were no significant differences in the serum levels of hormones, biochemical variables, or ovarian morphology between GG and non-GG genotypes. CONCLUSION(S) The ER-beta gene +1730 G/A polymorphism may be associated with pathophysiologic aberrancies involved in PCOS.
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Affiliation(s)
- Jin Ju Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, South Korea
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Kevenaar ME, Themmen APN, van Kerkwijk AJ, Valkenburg O, Uitterlinden AG, de Jong FH, Laven JSE, Visser JA. Variants in the ACVR1 gene are associated with AMH levels in women with polycystic ovary syndrome. Hum Reprod 2008; 24:241-9. [PMID: 18854405 DOI: 10.1093/humrep/den353] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Abstract
BACKGROUND Polycystic ovaries display an increased number of pre-antral and antral follicles compared with normal ovaries, suggesting that early and late follicle development are disturbed. The pathophysiology of this process is poorly understood. Since the transforming growth factor beta family members, anti-Müllerian hormone (AMH) and bone morphogenetic proteins (BMPs), inhibit FSH sensitivity, their signalling may contribute to the aberrant follicle development in these women. Here, we investigated the role of ALK2, a type I receptor for AMH/BMP signalling, in PCOS using a genetic approach. METHODS Seven single nucleotide polymorphisms in the ACVR1 gene, encoding ALK2, were genotyped in 359 PCOS patients and 30 normo-ovulatory and 3543 population-based control women, and haplotypes were determined. Subsequently, the association of ACVR1 variants with ovarian parameters and hormone levels was investigated. RESULTS The polymorphisms rs1220134, rs10497189 and rs2033962 and their corresponding haplotypes did not show different frequencies from controls, but were associated with AMH levels in PCOS women (P = 0.001, P = 0.002 and P = 0.007, respectively). Adjustment for follicle number revealed that the association with AMH levels was, in part, independent from follicle number, suggesting that variants in ACVR1 also influence AMH production per follicle. CONCLUSIONS Genetic variation within ACVR1 is associated with AMH levels and follicle number in PCOS women, suggesting that ALK2 signalling contributes to the disturbed folliculogenesis in PCOS patients.
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Affiliation(s)
- Marlies E Kevenaar
- Department of Internal Medicine, Erasmus MC, PO Box 2040, 3000 CA Rotterdam, The Netherlands
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Christopoulos P, Mastorakos G, Gazouli M, Panidis D, Deligeoroglou E, Katsikis I, Papadias K, Diamandi-Kandarakis E, Creatsas G. Genetic variants in TCF7L2 and KCNJ11 genes in a Greek population with polycystic ovary syndrome. Gynecol Endocrinol 2008; 24:486-490. [PMID: 18958766 DOI: 10.1080/09513590802196379] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/21/2022] Open
Abstract
Polycystic ovary syndrome (PCOS), the most common reproductive endocrine disorder of premenopausal women, is strongly associated with hyperinsulinemia and type 2 diabetes mellitus (T2DM). Given the phenotypic overlap between PCOS and T2DM, our objective was to investigate whether the TCF7L2 rs7903146(C/T) and the KCNJ11 E23K variants are involved in susceptibility to PCOS and related traits in a Greek population. A total of 183 PCOS patients and 148 healthy controls participated. All participants were Greeks. Blood was taken before hormonal therapy. PCOS patients and healthy controls were genotyped for the TCF7L2 and KCNJ11 variants. The T allele of the TCF7L2 rs7903146 variant was found to be marginally over-represented in Greek patients with PCOS. There was no association between KCNJ11 E23K polymorphism and PCOS in the present study. In addition, there were no associations observed between hormone levels and insulin resistance in PCOS carriers of TCF7L2 rs7903146 and KCNJ11 E23K variants. These data provide evidence that the rs7903146 variant of the TCF7L2 gene might influence PCOS predisposition, while no association is observed between the E23K variant of KCNJ11 and susceptibility to PCOS and related traits.
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Affiliation(s)
- Panagiotis Christopoulos
- Second Department of Obstetrics and Gynecology, School of Medicine, University of Athens, Athens, Greece.
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Liu Q, Gu W, Cui B, Hong J, Zhang Y, Chi Z, Su Y, Ning G. The association of TAAAAn repeat polymorphism in sex hormone-binding protein gene with polycystic ovary syndrome in Chinese population. Endocrine 2008; 34:62-7. [PMID: 18937076 DOI: 10.1007/s12020-008-9104-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/17/2008] [Revised: 08/30/2008] [Accepted: 09/08/2008] [Indexed: 12/13/2022]
Abstract
TAAAAn polymorphism in sex hormone-binding globulin (SHBG) gene has been found to influence the transcriptional activity of SHBG gene in vitro, and several studies have reported variable associations of this polymorphism with serum SHBG levels in women with polycystic ovary syndrome (PCOS). We have investigated the association of TAAAAn polymorphism with PCOS in 187 women with PCOS and 176 controls; in which five alleles (6-10 repeats) and 13 genotypes were found. None of the TAAAAn alleles or genotypes occurred in significant different frequency in PCOS patients compared with controls. Serum SHBG in the PCOS group was significantly lower than those in controls (33.8 +/- 30.2 nmol/l vs. 65.58 +/- 31.12 nmol/l; P < 0.01). Serum SHBG concentrations were similar for patients with PCOS whether they displayed short or long genotypes for TAAAAn (Log10SHBG: 1.46 +/- 0.38 and 1.58 +/- 0.33, respectively). Similar results were observed for controls (Log10SHBG: 1.79 +/- 0.17 and 1.77 +/- 0.14, respectively). In contrast, serum SHBG values were negatively associated with body mass index (BMI) and homeostasis model assessment of insulin resistance in the PCOS group (B = -0.285 and -0.264, respectively; P < 0.01). Thus, the TAAAAn polymorphism in SHBG gene was not a determinant of PCOS in this population of Chinese women, whereas, serum SHBG was significantly associated with BMI and insulin resistance in these PCOS patients.
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Affiliation(s)
- Qiaorui Liu
- Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai Institute of Endocrinology and Metabolism, Department of Endocrine and Metabolic Diseases, Shanghai JiaoTong University School of Medicine, Shanghai, People's Republic of China
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45
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Kim JJ, Choung SH, Choi YM, Yoon SH, Kim SH, Moon SY. Androgen receptor gene CAG repeat polymorphism in women with polycystic ovary syndrome. Fertil Steril 2008; 90:2318-23. [PMID: 18191848 DOI: 10.1016/j.fertnstert.2007.10.030] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2007] [Revised: 10/25/2007] [Accepted: 10/25/2007] [Indexed: 12/20/2022]
Abstract
OBJECTIVE To evaluate the role of the androgen receptor (AR) gene CAG repeat in women with polycystic ovary syndrome (PCOS). DESIGN Case control study. SETTING University department of obstetrics and gynecology. PATIENT(S) Women with (n = 114) or without (n = 205) PCOS. INTERVENTION(S) Peripheral blood sampling was done for DNA analysis and serum hormone measurements. MAIN OUTCOME MEASURE(S) CAG repeat length and serum androgen levels. RESULT(S) No statistically significant CAG repeat length differences were found between patients and controls. We conducted a detailed analysis after dividing PCOS patients according to their free testosterone levels. The high free testosterone group had a statistically significantly longer mean biallelic average (24.0 +/- 2.0 vs. 23.0 +/- 1.5), short (22.5 +/- 1.8 vs. 21.7 +/- 1.9), and long (25.5 +/- 2.9 vs. 24.4 +/- 1.9) allelic lengths than the normal free testosterone group. In PCOS patients, a statistically significant correlation was found between biallelic average length and free testosterone concentration, either unadjusted or after adjustment. CONCLUSION(S) The AR gene CAG repeat polymorphism may contribute to the serum concentration of free testosterone in PCOS patients. A subset of PCOS patients with relatively longer CAG repeats (less AR activity) tended to show a higher serum androgen concentration.
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Affiliation(s)
- Jin Ju Kim
- Department of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, South Korea
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Affiliation(s)
- Atilla Büyükgebiz
- Department of Pediatric Endocrinology, Acibadem Hospital, Istanbul, Turkey.
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Schröer A, Vogt P, Griesinger G, Fischer D, Diedrich K, Strowitzki T. Genetik ovarieller Störungen. GYNAKOLOGISCHE ENDOKRINOLOGIE 2007. [DOI: 10.1007/s10304-006-0171-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
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Ferk P, Teran N, Gersak K. The (TAAAA)n microsatellite polymorphism in the SHBG gene influences serum SHBG levels in women with polycystic ovary syndrome. Hum Reprod 2006; 22:1031-6. [PMID: 17189294 DOI: 10.1093/humrep/del457] [Citation(s) in RCA: 52] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Hyperandrogenaemia is a common feature of polycystic ovary syndrome (PCOS). The sex hormone-binding globulin (SHBG) gene was proposed as being a PCOS candidate gene. A possible influence of the microsatellite polymorphism (TAAAA)(n) in the SHBG gene on serum SHBG levels in PCOS patients was investigated. METHODS One hundred and twenty-three PCOS patients and 110 age-matched controls were included in the study. Peripheral blood samples were obtained. Genotyping of the (TAAAA)(n) polymorphism in the SHBG gene was performed. Serum LH, FSH, SHBG and total testosterone concentrations were determined. RESULTS SHBG alleles with 6-11 TAAAA repeats were found. None of the SHBG alleles or genotypes were present at a significantly more frequent rate in PCOS patients compared with controls. Serum SHBG levels were significantly lower (P < 0.001) in PCOS patients compared with controls and were found to be strongly influenced by the (TAAAA)(n) SHBG polymorphism, in both the PCOS (55.3%) and control (33.1%) groups of patients. CONCLUSIONS The (TAAAA)(n) SHBG gene polymorphism might be an important predictor for serum SHBG levels and, consequently, for hyperandrogenaemic clinical presentation of PCOS.
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Affiliation(s)
- Polonca Ferk
- Department of Obstetrics and Gynaecology, Division of Medical Genetics, University Medical Centre, Ljubljana, Slovenia
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Abstract
By participating in pathways of cholesterol biosynthesis and elimination, different cytochrome P450 (P450 or CYP) enzymes play an important role in maintenance of cholesterol homeostasis. CYP51 is involved in cholesterol biosynthesis, whereas CYP 7A1, 27A1, 46A1, 7B1, 39A1, and 8B1 are the key enzymes in cholesterol catabolism to bile acids, the major route of cholesterol elimination in mammals. Cholesterol transformations to steroid hormones are also initiated by the P450 enzyme CYP11A1. Finally, one of the major drug-metabolizing P450s CYP3A4 seems to contribute to bile acid biosynthesis as well. The 9 P450s will be the focus of this review and assessed as drug targets for cholesterol lowering.
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Affiliation(s)
- Irina A Pikuleva
- Department of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Boulevard, Galveston, TX 77555-1031, USA.
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Sorensen MB, Franks S, Robertson C, Pennell DJ, Collins P. Severe endothelial dysfunction in young women with polycystic ovary syndrome is only partially explained by known cardiovascular risk factors. Clin Endocrinol (Oxf) 2006; 65:655-9. [PMID: 17054469 DOI: 10.1111/j.1365-2265.2006.02645.x] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
OBJECTIVE We aimed to assess whether metabolic abnormalities can explain endothelial dysfunction and associated cardiovascular disease risk (CVDr) in polycystic ovary syndrome (PCOS). Endothelial function, a recognized composite marker of CVDr, may be reduced in PCOS and can be precisely and noninvasively assessed by cardiovascular magnetic resonance (CMR). PATIENTS Fourteen women with anovulatory PCOS (age [mean +/- SD] 33 +/- 4 years) and 13 controls (age: 33 +/- 6 years) with similar body mass index and regular menses. METHODS Endothelium-dependent (flow-mediated dilatation - FMD) and -independent (glyceryl trinitrate - GTN) changes in the brachial artery area were measured using CMR in women with PCOS and controls. Arterial function was assessed twice, in the early follicular phase and mid cycle in controls and after an interval of 2 weeks in PCOS subjects. Fasting lipids, glucose, insulin and sex hormones were measured at the first visit. RESULTS FMD was greatly reduced in women with PCOS compared to controls (-1%vs 5% and 2%vs 12%, P < 0.01) without differences in GTN responses. Risk factors were more prevalent in PCOS women and displayed significant linear relationships with FMD. PCOS status was the strongest predictor of FMD. Linear regression between PCOS and FMD remained significant after correction for all CVD risk markers linked to the metabolic syndrome. CONCLUSION PCOS is associated with changes in CVD risk markers and pronounced endothelial dysfunction. However endothelial dysfunction with PCOS is only partly explained by recognized CVD risk markers.
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Affiliation(s)
- Morten B Sorensen
- CMR Unit and Department of Cardiac Medicine, Imperial College London, Royal Brompton Hospital, London, UK
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