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Benameur T. Seasonal Variations in 25-Hydroxyvitamin D Levels among Pediatric Patients Attending the Healthcare Centre. Nutrients 2024; 16:379. [PMID: 38337664 PMCID: PMC10856968 DOI: 10.3390/nu16030379] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2023] [Revised: 01/17/2024] [Accepted: 01/24/2024] [Indexed: 02/12/2024] Open
Abstract
Vitamin D plays an essential role in maintaining bone density, building the immune system, and regulating cell growth alongside other key biological functions. Limited data are available about the seasonal variation in vitamin D levels in the pediatric population in Saudi Arabia. This study aimed to investigate the seasonal influence on the pediatric circulating levels of 25(OH)D. A total of 1790 pediatric outpatients who visited the University healthcare centre were included in this study. Overall, there was a noticeably high prevalence (69%) of both combined 25(OH)D deficiency and insufficiency. The highest mean serum concentration of 25(OH)D was recorded in summer (29 ng/mL) and autumn (27 ng/mL). The deficient and insufficient categories were predominant, accounting for 33% and 36%, respectively. Comparable patterns were recorded during autumn, winter, and spring. Interestingly, the 25(OH)D level was significantly associated with the four seasons (p = 0.001), with females having a higher prevalence of 25(OH)D deficiency in the spring and summer than males. Furthermore, only in autumn and winter, we found a significant association between gender and 25(OH)D status (p < 0.001 for both). Another association between nationality and the circulating levels 25(OH)D was found during autumn and winter (p < 0.001 and p = 0.01), respectively. In all seasons, age had a negative impact on serum (OH)D levels. However, this relationship was statistically significant (p < 0.05) only in summer, autumn, and winter. Gender was a significant predictor, with 25(OH)D levels in autumn and winter and an odds ratio of 1.67 in autumn and 2 in winter, indicating that being men had a positive influence on circulating 25(OH)D levels. There were highly significant differences in 25(OH)D concentrations among different age categories. The Saudi population experiences low levels of vitamin D, particularly in autumn and winter periods. This study showed that seasonality, age category, nationality, and gender influence vitamin D status, suggesting the need for tailored intervention and monitoring of 25(OH)D status to reach adequate levels of vitamin D. Healthcare practitioners and policymakers may consider the interplay between age, nationality, gender, and seasonal variations when addressing vitamin D status and a targeted supplementation approach for high-risk groups that may develop health issues.
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Affiliation(s)
- Tarek Benameur
- Department of Biomedical Sciences, College of Medicine, King Faisal University, Al Ahsa 31982, Saudi Arabia
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Benameur T, Kaliyadan F, Saidi N, Porro C. A Retrospective Chart Review Evaluating Changes in 25-Hydroxyvitamin D Levels among Patients Attending the University Healthcare Centre during the COVID-19 Pandemic. Nutrients 2023; 15:2345. [PMID: 37242228 PMCID: PMC10223421 DOI: 10.3390/nu15102345] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Revised: 05/10/2023] [Accepted: 05/12/2023] [Indexed: 05/28/2023] Open
Abstract
COVID-19-pandemic-related home confinement aids in limiting the spread of the virus but restricts exposure to sunlight, thereby possibly affecting 25(OH)D concentrations. This study aimed to investigate the effect of lockdown measures on 25(OH)D levels in outpatients visiting the healthcare centre over a period of two years. In this retrospective chart review, outpatients who visited a university healthcare centre for a health check-up over a period of two years were included. The patients' 25(OH)D serum levels and status were compared before, during, and after the lockdown periods. A total of 7234 patients were included in this study, with a mean age of 34.66 ± 16.78. The overall prevalence of 25(OH)D insufficiency, deficiency and sufficiency was 33.8%, 30.7% and 35.4%, respectively. The proportion of individuals with 25-(OH) D deficiency prior to lockdown was 29% and this proportion increased in the lockdown and post-lockdown periods to 31.1% and 32%, respectively. Although gender was less likely to have an impact on the 25 (OH) D level during the lockdown period (p = 0.630), we found an association between gender and 25 (OH) D status in the pre-lockdown and post-lockdown periods (p < 0.001 and p < 0.001, respectively). Another association between nationality and 25 (OH)D levels was found before, during and after the lockdown periods (p < 0.001). In addition, the youngest population, aged between 1 and 14, was strongly affected by the home confinement. Age had a positive and significant (p < 0.05) effect on 25 (OH) D status regardless of the different periods. Moreover, in the pre-lockdown period, male outpatients had 1.56 chance of having a sufficient level of 25 (OH)D. However, during the lockdown period, this chance decreased to 0.85 and then increased to 0.99 after the lockdown period. We found no statistically significant difference in the mean serum concentrations or in the prevalence of vitamin D insufficiency when we compared values from before, during and immediately after the COVID-19 lockdown period. However, there was a generally increased prevalence of vitamin D insufficiency in our study population. Another association between gender, nationality and age groups with 25(OH) D was found. Regular exposure to UVR is recommended for maintaining adequate vitamin D levels and to prevent vitamin D deficiency. Further research is needed to determine the best indications for vitamin D supplementation if confinement periods are extended and to consider the potential health consequences of prolonged confinement periods not only on vitamin D status but also on overall public health. The findings of this study may be considered by stakeholders for a targeted supplementation approach for risk groups.
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Affiliation(s)
- Tarek Benameur
- Department of Biomedical Sciences, College of Medicine, King Faisal University, Al Ahsa 31982, Saudi Arabia
| | - Feroze Kaliyadan
- Sree Narayana Institute of Medical Sciences, Kerala University of Health Sciences, Thrissur 683594, India
| | - Neji Saidi
- Department of Mathematics and Statistics, College of Sciences, King Faisal University, Al Ahsa 31982, Saudi Arabia
| | - Chiara Porro
- Department of Clinical and Experimental Medicine, University of Foggia, 71121 Foggia, Italy
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İnan-Erdoğan I, Akgül S, Işgın-Atıcı K, Tuğrul-Yücel T, Boduroğlu K, Derman O, Kanbur N. Effects of vitamin D and estrogen receptor polymorphisms on bone mineral density in adolescents with anorexia nervosa. J Pediatr Endocrinol Metab 2019; 32:1377-1384. [PMID: 31714887 DOI: 10.1515/jpem-2019-0240] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2019] [Accepted: 09/02/2019] [Indexed: 11/15/2022]
Abstract
Background Anorexia nervosa (AN) is a serious eating disorder that is associated with decreased bone mineral density (BMD) and greater lifetime risk for fractures. The aim of this study was to determine the correlation between BMD and genetic polymorphisms in AN. Methods This case-control study analyzed vitamin D receptor (VDR) (VDRBsml, VDRFokl) and estrogen receptor (ESR) (ESR1Xbal, ESR1Pvull) polymorphisms in 45 adolescents diagnosed with AN and 46 age-matched healthy controls. BMD values of the AN group were classified as low or normal, and polymorphisms were compared between cases and controls. The effects of body mass index (BMI), duration of disease and amenorrhea on BMD were also evaluated. Results In girls with AN, a positive effect of the bb genotype of VDRBsmI polymorphism on femur Z-scores (p = 0.103) and of the Ff genotype of VDRFokI polymorphism on vertebra Z-scores (p = 0.097) was observed. In boys with AN, a positive effect of the Ff genotype of VDRFokI polymorphism on vertebra BMD (g/cm2) was detected (p = 0.061). No association was detected between ESR polymorphisms. An inverse relationship was observed between BMD and duration of illness and amenorrhea. A direct relationship was detected between BMD and BMI. Conclusions Specific VDR gene polymorphism genotypes may have positive effects on BMD in patients with AN. Additionally, the lack of association between ESR gene polymorphisms on BMD could be attributed to the low estrogen status of the patient.
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Affiliation(s)
- Işıl İnan-Erdoğan
- Hacettepe University Faculty of Medicine, İhsan Doğramacı Children's Hospital, Department of Pediatrics, Ankara, Turkey
| | - Sinem Akgül
- Hacettepe University Faculty of Medicine, İhsan Doğramacı Children's Hospital, Department of Pediatrics, Division of Adolescent Medicine, Ankara, Turkey
| | - Kübra Işgın-Atıcı
- Hacettepe University, Department of Nutrition and Dietetics, Ankara, Turkey
| | - Tuğba Tuğrul-Yücel
- Hacettepe University Faculty of Medicine, İhsan Doğramacı Children's Hospital, Department of Pediatrics, Division of Pediatric Genetics, Ankara, Turkey
| | - Koray Boduroğlu
- Hacettepe University Faculty of Medicine, İhsan Doğramacı Children's Hospital, Department of Pediatrics, Division of Pediatric Genetics, Ankara, Turkey
| | - Orhan Derman
- Hacettepe University Faculty of Medicine, İhsan Doğramacı Children's Hospital, Department of Pediatrics, Division of Adolescent Medicine, Ankara, Turkey
| | - Nuray Kanbur
- Hacettepe University Faculty of Medicine, İhsan Doğramacı Children's Hospital, Department of Pediatrics, Division of Adolescent Medicine, Ankara, Turkey
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Fouda A, Kandil S, Boujettif K, Fayea N. Hypovitamininosis D in Childhood Cancer Survivors: Importance of Vitamin D Supplementation and Measurement Over Different Points of Time. J Pediatr Hematol Oncol 2018; 40:e83-e90. [PMID: 29240025 DOI: 10.1097/mph.0000000000001060] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
This observational retrospective cross-sectional and case-controlled study measures levels of 25-hydroxy-vitamin D (25-OH-VD) in pediatric cancer survivors at different intervals and assesses the effect of 2 supplementation regimens over a period of 12 months. Sixty-eight patients were included in this quasi-experimental study, of which 32 were boys and 36 were girls. A control group of 30 healthy children were included. It was found that initial 25-OH-VD levels were insufficient (<30 ng/mL) in 61 patients (89.7%). Yet, no significant difference between the levels of 25-OH-VD in these patients as compared with the healthy control group was evidenced. However, 25-OH-VD levels were significantly higher at 18 months in patients who were supplemented with oral 50,000 IU/month vitamin D during the 12 months in comparison with patients supplemented with 1000 IU/day. Our findings indicate that pediatric cancer survivors who require frequent monitoring of their 25-OH-VD levels yielded better results when supplemented with higher doses of vitamin D over longer periods of time. A course of oral vitamin D supplementation regimen of 50,000 IU/month gave effective results with excellent compliance and no reports of any adverse or harmful effects.
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Affiliation(s)
- Ashraf Fouda
- Mansoura University Children Hospital, Faculty of Medicine, Mansoura University, Al-Mansoura, Egypt
| | - Shaimaa Kandil
- Mansoura University Children Hospital, Faculty of Medicine, Mansoura University, Al-Mansoura, Egypt
| | | | - Najwa Fayea
- Jeddah Oncology Center, King Abdullah Medical City, Jeddah, Kingdom of Saudi Arabia
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Abstract
Osteoporosis is a descriptive term for a loss of bone mass and structure which predisposes to fracture in response to minimal trauma. These fractures cause pain, disability and significant mortality, with enormous resource costs to health and other services. Proximal femoral (hip) fractures account for most of the mortality and cost, and an estimated six million osteoporosis-related hip fractures occur world-wide each year, a number likely to increase dramatically due to changes in population demographics. The diagnosis of osteoporosis should be considered in all patients over the age of 50 years who sustain a fracture, unless there is obvious major trauma. Not only will this inform immediate management but it also allows measures aimed at prevention of further fractures to be implemented. Early surgery is often effective in limiting morbidity from osteoporotic fractures and in older people is best planned in collaboration with other health care professionals.
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Affiliation(s)
- FH Anderson
- University of Southampton, Southampton General Hospital, Southampton, UK
| | - C Cooper
- MRC Environmental Epidemiology Unit, Southampton General Hospital, Southampton, UK
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Nationality, Gender, Age, and Body Mass Index Influences on Vitamin D Concentration among Elderly Patients and Young Iraqi and Jordanian in Jordan. Biochem Res Int 2016; 2016:8920503. [PMID: 27110402 PMCID: PMC4823503 DOI: 10.1155/2016/8920503] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2015] [Revised: 02/10/2016] [Accepted: 02/23/2016] [Indexed: 11/17/2022] Open
Abstract
Vitamin D is necessary for maintaining and regulating calcium levels; thus, insufficiency of vitamin D increases the risk of many chronic diseases. This study aimed to examine vitamin D levels among Jordanian and Iraqi volunteers and find the relation between vitamin D level and lipid profile patients. Vitamin D levels were evaluated using enzyme-linked immunosorbent assay. For young healthy group subjects, vitamin D levels were 20.60 ± 5.94 ng/mL for Jordanian and 27.59 ± 7.74 ng/mL for Iraqi. Vitamin D concentrations for young males and females were 25.82 ± 8.33 ng/mL and 21.95 ± 6.39 ng/mL, respectively. Females wearing hijab were 20.87 ± 6.45 ng/mL, while uncovered females were 23.55 ± 6.04 ng/mL. For >40 years Iraqi subjects, vitamin D level for healthy was 29.78 ± 9.49 ng/mL and 23.88 ± 7.93 ng/mL for hyperlipidemic subjects. Vitamin D levels for overweight and obese healthy groups were significantly higher (P < 0.050) than those for the hyperlipidemic patients groups. Vitamin D levels for males were significantly higher than females and were significantly higher for healthy than those hyperlipidemic Iraqi patients. These findings showed that vitamin D levels are affected by age, nationality, gender, and health statues and highlight the importance of vitamin D supplementation for groups with low levels particularly old, hijab wearing females, and hyperlipidemic groups.
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Genetic polymorphisms of interleukin-1 alpha and the vitamin d receptor in mexican mestizo patients with intervertebral disc degeneration. Int J Genomics 2014; 2014:302568. [PMID: 25506053 PMCID: PMC4258367 DOI: 10.1155/2014/302568] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2014] [Accepted: 11/12/2014] [Indexed: 01/08/2023] Open
Abstract
Intervertebral disc degeneration (IDD) is the most common diagnosis in patients with back pain, a leading cause of musculoskeletal disability worldwide. Several conditions, such as occupational activities, gender, age, and obesity, have been associated with IDD. However, the development of this disease has strong genetic determinants. In this study, we explore the possible association between rs1800587 (c.-949C>T) of interleukin-1 alpha (IL1A) and rs2228570 (c.2T>V) and rs731236 (c.1056T>C) of vitamin D receptor (VDR) gene polymorphisms and the development of IDD in northwestern Mexican Mestizo population. Gene polymorphisms were analyzed by polymerase chain reaction followed by restriction fragment length polymorphism, in two groups matched by age and gender: patients with symptomatic lumbar IDD (n = 100) and subjects with normal lumbar-spine MRI-scans (n = 100). Distribution of the mutated alleles in patients and controls was 27.0% versus 28.0% (P = 0.455) for T of rs1800587 (IL1A); 53.0% versus 58.0% (P = 0.183) for V of rs2228570 (VDR); and 18.0% versus 21.0% (P = 0.262) for C of rs731236 (VDR). Our results showed no association between the studied polymorphisms and IDD in this population. This is the first report on the contribution of gene polymorphisms on IDD in a Mexican population.
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Mohammadi Z, Fayyazbakhsh F, Ebrahimi M, Amoli MM, Khashayar P, Dini M, Zadeh RN, Keshtkar A, Barikani HR. Association between vitamin D receptor gene polymorphisms (Fok1 and Bsm1) and osteoporosis: a systematic review. J Diabetes Metab Disord 2014; 13:98. [PMID: 25364703 PMCID: PMC4215021 DOI: 10.1186/s40200-014-0098-x] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2014] [Accepted: 09/30/2014] [Indexed: 01/01/2023]
Abstract
Osteoporosis is a health concern characterized by reduced bone mineral density (BMD) and increased risk of fragility fractures. Many studies have investigated the association between genetic variants and osteoporosis. Polymorphism and allelic variations in the vitamin D receptor gene (VDR) have been found to be associated with bone mineral density. However, many studies have not been able to find this association. Literature review was conducted in several databases, including MEDLINE/Pubmed, Scopus, EMBASE, Ebsco, Science Citation Index Expanded, Ovid, Google Scholar, Iran Medex, Magiran and Scientific Information Database (SID) for papers published between 2000 and 2013 describing the association between Fok1 and Bsm1 polymorphisms of the VDR gene and osteoporosis risk. The majority of the revealed papers were conducted on postmenopausal women. Also, more than 50% studies reported significant relation between Fok1, Bsm1 and osteoporosis. Larger and more rigorous analytical studies with consideration of gene-gene and gene-environment interactions are needed to further dissect the mechanisms by which VDR polymorphisms influence osteoporosis.
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Affiliation(s)
- Zahra Mohammadi
- />Department of biology, Damghan branch, Islamic Azad University, Damghan, Iran
| | - Fateme Fayyazbakhsh
- />Osteoporosis Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- />Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mehdi Ebrahimi
- />Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahsa M Amoli
- />Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- />Biomedical Engineering Department, Maziar University, Rouyan, Iran
- />EMRI, Dr Shariati Hospital, North Karegar St., Tehran, 14114 Iran
| | - Patricia Khashayar
- />Osteoporosis Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- />Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahboubeh Dini
- />Non-communicable Disease Department, Iran Ministry of Health and Medical Education, Tehran, Iran
| | - Reza Nezam Zadeh
- />Department of biology, Damghan branch, Islamic Azad University, Damghan, Iran
| | - Abbasali Keshtkar
- />Osteoporosis Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- />Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Hamid Reza Barikani
- />Dental Implant Research Center, Tehran University of Medical Sciences, Tehran, Iran
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Mayer JE, Iatridis JC, Chan D, Qureshi SA, Gottesman O, Hecht AC. Genetic polymorphisms associated with intervertebral disc degeneration. Spine J 2013; 13:299-317. [PMID: 23537453 PMCID: PMC3655694 DOI: 10.1016/j.spinee.2013.01.041] [Citation(s) in RCA: 155] [Impact Index Per Article: 12.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/07/2011] [Revised: 01/02/2013] [Accepted: 01/25/2013] [Indexed: 02/03/2023]
Abstract
BACKGROUND CONTEXT Disc degeneration (DD) is a multifaceted chronic process that alters the structure and function of the intervertebral discs and can lead to painful conditions. The pathophysiology of degeneration is not well understood, but previous studies suggest that certain genetic polymorphisms may be important contributing factors leading to an increased risk of DD. PURPOSE To review the genetic factors in DD with a focus on polymorphisms and their putative role in the pathophysiology of degeneration. Elucidating the genetic components that are associated with degeneration could provide insights into the mechanism of the process. Furthermore, defining these relationships and eventually using them in a clinical setting may allow an identification and early intervention for those who are at a high risk for painful DD. STUDY DESIGN Literature review. METHODS This literature review focused on the studies concerning genetic polymorphisms and their associations with DD. RESULTS Genetic polymorphisms in 20 genes have been analyzed in association with DD, including vitamin D receptor, growth differentiation factor 5 (GDF5), aggrecan, collagen Types I, IX, and XI, fibronectin, hyaluronan and proteoglycan link protein 1 (HAPLN1), thrombospondin, cartilage intermediate layer protein (CILP), asporin, MMP1, 2, and 3, parkinson protein 2, E3 ubiquitin protein ligase (PARK2), proteosome subunit β type 9 (PSMB9), tissue inhibitor of metalloproteinase (TIMP), cyclooxygenase-2 (COX2), and IL1α, IL1β, and IL6. Each genetic polymorphism codes for a protein that has a functional role in the pathogenesis of DD. CONCLUSIONS There are known associations between several genetic polymorphisms and DD. Of the 20 genes analyzed, polymorphisms in vitamin D receptor, aggrecan, Type IX collagen, asporin, MMP3, IL1, and IL6 show the most promise as functional variants. Genetic studies are crucial for understanding the mechanism of the degeneration. This genetic information could eventually be used as a predictive model for determining a patient's risk for symptomatic DD.
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Affiliation(s)
- Jillian E. Mayer
- Leni and Peter W May Department of Orthopaedics, Mount Sinai Medical Center, 5 East 98th Street, 9th Floor, New York, NY 10029, USA
| | - James C. Iatridis
- Leni and Peter W May Department of Orthopaedics, Mount Sinai Medical Center, 5 East 98th Street, 9th Floor, New York, NY 10029, USA
| | - Danny Chan
- Department of Biochemistry, The University of Hong Kong, Pokfulam, Hong Kong SAR, China
| | - Sheeraz A. Qureshi
- Leni and Peter W May Department of Orthopaedics, Mount Sinai Medical Center, 5 East 98th Street, 9th Floor, New York, NY 10029, USA
| | - Omri Gottesman
- Institute for Personalized Medicine, Mount Sinai Medical Center, 1468 Madison Avenue, 18th Floor, New York, NY 10029, USA
| | - Andrew C. Hecht
- Leni and Peter W May Department of Orthopaedics, Mount Sinai Medical Center, 5 East 98th Street, 9th Floor, New York, NY 10029, USA,Corresponding Author: Andrew C. Hecht, Mount Sinai Medical Center. 5 East 98 Street, 9 Floor, New York, NY 10029, USA. Tel: (212) 241-8892; Fax: (212) 423-0827.
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Allelic variations in coding regions of the vitamin D receptor gene in dairy cows and potential susceptibility to periparturient hypocalcaemia. J DAIRY RES 2012; 79:423-8. [DOI: 10.1017/s0022029912000465] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Periparturient hypocalcaemia (milk fever) is a disorder of Ca metabolism in dairy cattle primarily affecting multiparous cows. The major reasons for the rapid decrease of blood Ca concentration after calving are the prompt increase of Ca secretion into the colostrum and the delayed activation of Ca regulation mechanisms including calcitriol, a metabolite of vitamin D. In man, vitamin D receptor (VDR) gene polymorphisms are reported to be associated with disturbances of Ca metabolism, whereas data confirming the same in dairy cows are still missing. Moreover, polymorphisms that only affect non-coding regions are sometimes difficult to ascribe to a specific disorder as pathways and unequivocal links remain elusive. Therefore, the idea of the present study was to investigate in a small group of dairy cows with documented clinical records whether polymorphisms in the coding regions of the VDR gene existed and whether these potentially found variations were correlated with the incidence of periparturient hypocalcaemia. For this purpose, blood DNA was isolated from 26 dairy cows in their 4th to 6th lactation, out of which 17 had experienced hypocalcaemia at least once, whereas 9 cows had never undergone periparturient hypocalcaemia in their lifetime. The 10 VDR exons and small parts of adjacent introns were sequenced and compared with the Bos taurus VDR sequence published on NCBI based on the DNA of one Hereford cow. In total, 8 sequence alterations were detected in the fragments, which were primarily heterozygous. However, only 4 of them were really located on exons thereby potentially causing changes of the encoded amino acid of the VDR protein, but were not correlated with the incidence of periparturient hypocalcaemia. Certainly, this lack of statistical correlation could be due to the small number of animals included; anyhow, it was not encouraging enough to initiate a larger study with hundreds of cows and document blood Ca levels post partum for at least four lactations.
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Tea and coffee consumption in relation to vitamin D and calcium levels in Saudi adolescents. Nutr J 2012; 11:56. [PMID: 22905922 PMCID: PMC3478213 DOI: 10.1186/1475-2891-11-56] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2012] [Accepted: 08/11/2012] [Indexed: 12/28/2022] Open
Abstract
BACKGROUND Coffee and tea consumption was hypothesized to interact with variants of vitamin D-receptor polymorphisms, but limited evidence exists. Here we determine for the first time whether increased coffee and tea consumption affects circulating levels of 25-hydroxyvitamin D in a cohort of Saudi adolescents. METHODS A total of 330 randomly selected Saudi adolescents were included. Anthropometrics were recorded and fasting blood samples were analyzed for routine analysis of fasting glucose, lipid levels, calcium, albumin and phosphorous. Frequency of coffee and tea intake was noted. 25-hydroxyvitamin D levels were measured using enzyme-linked immunosorbent assays. RESULTS Improved lipid profiles were observed in both boys and girls, as demonstrated by increased levels of HDL-cholesterol, even after controlling for age and BMI, among those consuming 9-12 cups of coffee/week. Vitamin D levels were significantly highest among those consuming 9-12 cups of tea/week in all subjects (p-value 0.009) independent of age, gender, BMI, physical activity and sun exposure. CONCLUSION This study suggests a link between tea consumption and vitamin D levels in a cohort of Saudi adolescents, independent of age, BMI, gender, physical activity and sun exposure. These findings should be confirmed prospectively.
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Al-Othman A, Al-Musharaf S, Al-Daghri NM, Krishnaswamy S, Yusuf DS, Alkharfy KM, Al-Saleh Y, Al-Attas OS, Alokail MS, Moharram O, Sabico S, Chrousos GP. Effect of physical activity and sun exposure on vitamin D status of Saudi children and adolescents. BMC Pediatr 2012; 12:92. [PMID: 22759399 PMCID: PMC3407533 DOI: 10.1186/1471-2431-12-92] [Citation(s) in RCA: 96] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2012] [Accepted: 07/03/2012] [Indexed: 01/09/2023] Open
Abstract
Background Accumulating evidence suggests an increased prevalence of vitamin D deficiency in the Middle East. In this context, we aimed to determine whether the prevalence of vitamin D deficiency is related to degree of physical activity and sun exposure among apparently healthy Saudi children and adolescents, a little studied population. Methods A total of 331 Saudi children aged 6–17 years (153 boys and 178 girls) were included in this cross sectional study. Levels of physical activity and sun exposure were determined using a standard questionnaire. Anthropometry, serum calcium and 25-(OH) vitamin D were analyzed. Results All subjects were vitamin D deficient, the majority being moderately deficient (71.6%). Age was the single most significant predictor affecting 25 (OH) Vitamin D levels, explaining 21% of the variance perceived (p = 1.68 x 10-14). Age-matched comparisons revealed that for groups having the same amount of sun exposure, those with moderate or are physically active will have higher levels of vitamin D status, though levels in across groups remained deficient. Conclusion Vitamin D deficiency is common among Saudi children and adolescents, and is influenced by both sun exposure and physical activity. Promotion of an active outdoor lifestyle among Saudi children in both homes and schools may counteract the vitamin D deficiency epidemic in this vulnerable population. Vitamin D supplementation is suggested in all groups, including those with the highest sun exposure and physical activity.
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Affiliation(s)
- Abdulaziz Al-Othman
- Prince Mutaib Chair for Biomarkers of Osteoporosis, King Saud University, Riyadh, Kingdom of Saudi Arabia
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Vivanco-Muñoz N, Jo T, Gerardo HB, Juan T, Clark P. Physical activity and dark skin tone: protective factors against low bone mass in Mexican men. J Clin Densitom 2012; 15:374-9. [PMID: 22698631 DOI: 10.1016/j.jocd.2012.03.007] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2011] [Revised: 03/16/2012] [Accepted: 03/19/2012] [Indexed: 11/23/2022]
Abstract
A cross-sectional study was conducted on 268 Mexican men between the ages of 13 and 80 yr to evaluate the association of clinical factors related with bone mass. Men from high schools, universities, and retirement homes were invited to participate. Body mass index (BMI) was measured, and bone mineral density (BMD) was assessed using dual-energy X-ray absorptiometry for L1-L4 and total hip. Factors related to bone mass were assessed by questionnaire and analyzed using a logistic regression model. Demographic factors (age, education, and occupation), clinical data (BMI, skin tone, previous fracture, history of osteoporosis [OP], and history of fractures), and lifestyle variables (diet, physical activity, sun exposure, and smoking) were evaluated. Physical activity (≥ 60 min/5 times a week) reduced the risk for low BMD for age, osteopenia, and OP at the spine and total hip (odds ratio [OR]: 0.276; 95% confidence interval [CI]: 0.099-0.769; p=0.014; and OR: 0.184; 95% CI: 0.04-0.849; p=0.03, respectively). Dark skin tone was a protective factor, decreasing the risk by up to 70%. In this population of healthy Mexican men (aged 13-80 yr), dark skin and physical activity were protective factors against low bone mass.
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Affiliation(s)
- Nalleli Vivanco-Muñoz
- Clinical Epidemiology Unit, Hospital Infantil de México "Federico Gómez"-Facultad de Medicina UNAM, Mexico City, Mexico
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14
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Pei FH, Wang YJ, Gao SL, Liu BR, DU YJ, Liu W, Yu HY, Zhao LX, Chi BR. Vitamin D receptor gene polymorphism and ulcerative colitis susceptibility in Han Chinese. J Dig Dis 2011; 12:90-8. [PMID: 21401893 DOI: 10.1111/j.1751-2980.2011.00483.x] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Specific polymorphisms in the vitamin D receptor (VDR) gene have been associated with genetic susceptibility to inflammatory bowel disease (IBD) in different ethnic populations. METHODS A total of 218 ulcerative colitis (UC) patients and 251 healthy controls were genotyped for VDR gene polymorphisms using PCR-restriction fragment length polymorphism (PCR-RFLP) assay. VDR gene polymorphisms (Apa I, Taq I, Bsm I and Fok I) were analyzed for both genotypic and phenotypic susceptibilities. RESULTS Among the four examined VDR gene polymorphisms, the Bsm I polymorphism showed a slightly higher distribution in our study population than that in the previous studies. We also found that the increased frequency of the Bb genotype of the Bsm I VDR gene polymorphism was associated with UC in Han Chinese, as compared with healthy controls (28.4% vs. 18.7%, χ(2) = 6.044, P = 0.014, OR = 1.739, 95% CI = 1.122-2.697). Moreover, Bsm I polymorphic allele (B) frequency was significantly increased in the UC cases, as compared to the healthy controls (14.7% vs. 7.8% χ(2) = 6.222, P = 0.013; OR = 1.670, 95% CI = 1.113-2.506). In contrast, the other three VDR gene polymorphisms (Apa I, Taq I and Fok I) were not associated with UC susceptibility in the Han Chinese cohort. In addition, none of these four VDR polymorphisms had statistical association with clinicopathological parameters of these UC patients. CONCLUSION This study demonstrated a probable association of the Bsm I polymorphism of the VDR gene with ulcerative colitis susceptibility in Han Chinese.
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Affiliation(s)
- Feng Hua Pei
- Department of Gastroenterology, The First Hospital of Jilin University, Changchun, Jilin Province, China
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15
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Abstract
Minerals are essential and toxic elements that have an impact on human health. Although we have learned a tremendous amount about the metabolism, biological roles, and health effects of minerals with the tools of biochemistry, cell biology, and molecular genetics, there are gaps in our knowledge of mineral biology that will benefit from new approaches. Forward genetics, whereby variations in phenotypes are mapped to natural genetic variation in the genome, has been successfully used to increase our understanding of many biologically important traits but has not yet been used extensively for mineral metabolism. In addition, the well-appreciated existence of interactions between minerals justifies a broader, systems approach to the study of mineral metabolism, i.e., ionomics. This short review will explain the value of forward genetics and ionomics as tools for exploring mammalian mineral metabolism.
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Affiliation(s)
- James C. Fleet
- Department of Foods and Nutrition, Department of Horticulture and Landscape Architecture, Purdue University, West Lafayette, IN 47906,Center for Gene-Environment Interactions, Department of Horticulture and Landscape Architecture, Purdue University, West Lafayette, IN 47906,To whom correspondence should be addressed. E-mail:
| | - Rebecca Replogle
- Department of Foods and Nutrition, Department of Horticulture and Landscape Architecture, Purdue University, West Lafayette, IN 47906
| | - David E. Salt
- Center for Gene-Environment Interactions, Department of Horticulture and Landscape Architecture, Purdue University, West Lafayette, IN 47906
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16
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Genomic and metabolomic patterns segregate with responses to calcium and vitamin D supplementation. Br J Nutr 2010; 105:71-9. [DOI: 10.1017/s0007114510003065] [Citation(s) in RCA: 43] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Inter-individual response differences to vitamin D and Ca supplementation may be under genetic control through vitamin D and oestrogen receptor genes, which may influence their absorption and/or metabolism. Metabolomic studies on blood and urine from subjects supplemented with Ca and vitamin D reveal different metabolic profiles that segregate with genotype. Genotyping was performed for oestrogen receptor 1 gene (ESR1) and vitamin D receptor gene (VDR) in fifty-six postmenopausal women. Thirty-six women were classified as low bone density as determined by a heel ultrasound scan and twenty women had normal bone density acting as ‘controls’. Those with low bone density (LBD) were supplemented with oral Ca and vitamin D and were classified according to whether they were ‘responders’ or ‘non-responders’ according to biochemical results before and after therapy compared to controls receiving no supplementation. Metabolomic studies on serum and urine were done for the three groups at 0 and 3 months of therapy using NMR spectroscopy with pattern recognition. The ‘non-responder’ group showed a higher frequency of polymorphisms in the ESR1 (codons 10 and 325) and VDR (Bsm1 and Taq1), compared with to the ‘responders’. The wild-type genotype for Fok1 was more frequent in those with LBD (70 %) compared with the control group (10 %). Distinctive patterns of metabolites were displayed by NMR studies at baseline and 3 months of post-treatment, segregating responders from non-responders and controls. Identification of potential ‘non-responders’ to vitamin D and Ca, before therapy, based on a genomic and/or metabolomic profile would allow targeted selection of optimal therapy on an individual basis.
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17
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Egan JB, Thompson PA, Vitanov MV, Bartik L, Jacobs ET, Haussler MR, Gerner EW, Jurutka PW. Vitamin D receptor ligands, adenomatous polyposis coli, and the vitamin D receptor FokI polymorphism collectively modulate beta-catenin activity in colon cancer cells. Mol Carcinog 2010; 49:337-52. [PMID: 20043299 DOI: 10.1002/mc.20603] [Citation(s) in RCA: 62] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
The activity of beta-catenin, commonly dysregulated in human colon cancers, is inhibited by the vitamin D receptor (VDR), and this mechanism is postulated to explain the putative anti-cancer activity of vitamin D metabolites in the colon. We investigated the effect of a common FokI restriction site polymorphism (F/f) in the human VDR gene as well as the effect of anti-tumorigenic 1,25-dihydroxyvitamin D(3) (1,25D) and pro-tumorigenic lithocholic acid (LCA) VDR ligands on beta-catenin transcriptional activity. Furthermore, the influence of a major regulatory protein of beta-catenin, the APC tumor suppressor gene, on VDR-dependent inhibition of beta-catenin activity was examined. We report herein that beta-catenin-mediated transcription is most effectively suppressed by the VDR FokI variant F/M4 when 1,25D is limiting. Using Caco-2 colorectal cancer (CRC) cells, it was observed that VDR ligands, 1,25D and LCA, both suppress beta-catenin transcriptional activity, though 1,25D exhibited significantly greater inhibition. Moreover, 1,25D, but not LCA, suppressed endogenous expression of the beta-catenin target gene DKK-4 independent of VDR DNA-binding activity. These results support beta-catenin sequestration away from endogenous gene targets by 1,25D-VDR. This activity is most efficiently mediated by the FokI gene variant F/M4, a VDR allele previously associated with protection against CRC. Interestingly, we found the inhibition of beta-catenin activity by 1,25D-VDR was significantly enhanced by wild-type APC. These results reveal a previously unrecognized role for 1,25D-VDR in APC/beta-catenin cross talk. Collectively, these findings strengthen evidence favoring a direct effect on the Wnt-signaling molecule beta-catenin as one anti-cancer target of 1,25D-VDR action in the colorectum.
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Affiliation(s)
- Jan B Egan
- Arizona Cancer Center, University of Arizona, Tucson, Arizona, USA
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18
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Ozaydin E, Dayangac-Erden D, Erdem-Yurter H, Derman O, Coşkun T. The relationship between vitamin D receptor gene polymorphisms and bone density, osteocalcin level and growth in adolescents. J Pediatr Endocrinol Metab 2010; 23:491-6. [PMID: 20662348 DOI: 10.1515/jpem.2010.080] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND/OBJECTIVE The relationship between vitamin D receptor gene polymorphisms and bone density, osteocalcin and growth was investigated. SUBJECTS Eighty eight adolescents aged between 8-15, with no history of illness influencing the level of bone parameters, were examined in our study. METHODS Areal BMD for lumbar spine (L1-4) was assessed by dual energy X-ray absorptiometry (DEXA). Height and weight were measured on the day of the DEXA scans. Serum osteocalcin level was determined by using ELISA method. DNA was extracted from white blood cells, amplified by the polymerase chain reaction (PCR) and the polymorphic sites were analyzed by using ApaI, TaqI and FokI restriction enzymes. RESULTS The most frequent genotypes were FF (% 54.6), Aa (% 53.4) and Tt (% 48.8). No significant relationship was found between VDR genotypes and areal BMD, osteocalcin level or growth in either sex. But there was a strong tendency for a higher BMD at the lumbar spine of TT and AA genotypes compared to tt and Aa genotypes. The children with TT genotype were taller and heavier than the children with tt genotype CONCLUSION Our results suggest that VDR gene TaqI polymorphism may be associated with body weight and bone mass, but more studies with larger groups should be conducted.
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Affiliation(s)
- Eda Ozaydin
- Health Ministry Ankara Diskapi Children's Hospital, Infancy Service, Turkey.
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19
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Naderi N, Farnood A, Habibi M, Derakhshan F, Balaii H, Motahari Z, Agah MR, Firouzi F, Rad MG, Aghazadeh R, Zojaji H, Zali MR. Association of vitamin D receptor gene polymorphisms in Iranian patients with inflammatory bowel disease. J Gastroenterol Hepatol 2008; 23:1816-22. [PMID: 18752562 DOI: 10.1111/j.1440-1746.2008.05525.x] [Citation(s) in RCA: 64] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND AND AIMS The vitamin D receptor (VDR) gene maps to a region on chromosome 12 shown to be linked to inflammatory bowel disease (IBD). Many studies have recognized the relation of VDR gene polymorphisms with inflammatory and autoimmune disorders. Determining the frequency of these polymorphisms and their possible relation with IBD can improve understandings about the genetic background of these diseases. The objective of this study was to assess the association of VDR gene polymorphisms (Apa I, Taq I, Bsm I, Fok I) with IBD in Iran. METHODS In this case control designed study 150 patients with ulcerative colitis, 80 patients with Crohn's disease and 150 Age and Sex matched healthy controls from Iranian origin were enrolled. These patients were referred to a tertiary center during a two-year period (2004-2006). Assessment of VDR gene polymorphisms was performed by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The genotype-phenotype association for these polymorphisms was analyzed. RESULTS Only the frequency of the Fok I polymorphism was significantly higher in ulcerative colitis and Crohn's groups. The frequency of the polymorphic allele f was higher in ulcerative colitis and Crohn's patients comparing with controls (P = 0.011 and P < 0.001, respectively). The f/f genotype was also significantly more frequent (P < 0.001), while the F/F genotype was less presented in Crohn's patients compared to controls (P < 0.001). No genotype-phenotype association was observed with any mutations. CONCLUSIONS This study suggests a probable association of the Fok I polymorphism in VDR receptor gene and Crohn's susceptibility in Iranian population.
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Affiliation(s)
- Nosratollah Naderi
- Research Center for Gastroenterology and Liver Diseases, Shahid Beheshti University, MC, Tehran, Iran
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20
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Bezerra FF, Cabello GMK, Mendonça LMC, Donangelo CM. Bone mass and breast milk calcium concentration are associated with vitamin D receptor gene polymorphisms in adolescent mothers. J Nutr 2008; 138:277-81. [PMID: 18203891 DOI: 10.1093/jn/138.2.277] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023] Open
Abstract
Lactation-associated bone loss has been reported in adolescent mothers. Polymorphisms in the vitamin D receptor (VDR) gene may contribute to differences in the physiologic skeletal response to lactation in these mothers. We evaluated the influence of VDR gene polymorphisms ApaI, BsmI, and TaqI on bone mass, bone and calcium-related hormones, and breast milk calcium of lactating adolescents with habitually low calcium intake. Total body bone mineral content (TBMC), total body bone mineral density (TBMD), lumbar spine BMD (LSBMD), serum hormones [intact parathyroid hormone (iPTH), 25-hydroxyvitamin D, insulin-like growth factor-I (IGF1), prolactin, and estradiol), and breast milk calcium were measured in 40 lactating Brazilian adolescents (15-18 y), and compared by VDR genotype subgroups after adjustment for calcium intake and postmenarcheal and lactational periods. TBMD and LSBMD Z scores were -0.55 +/- 1.01 and -1.15 +/- 1.48, respectively. LSBMD was higher (21%; P < 0.05) in adolescents with the aa genotype (n = 5) compared with those with the AA genotype (n = 7). TBMC and IGF1 were higher (23 and 50%, respectively; P < 0.05) in adolescents with tt (n = 4) than those with TT (n = 29) and Tt (n = 7) genotypes. Breast milk calcium and serum iPTH were higher (24 and 80%, respectively; P < 0.05) in adolescents with bb (n = 8) compared with those with BB (n = 21) genotype. These results indicate that bone mass and breast milk calcium are significantly associated with VDR genotypes in lactating Brazilian adolescents. Those with aa and tt genotypes had a better bone status and those with bb genotype had greater breast milk calcium.
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Affiliation(s)
- Flávia F Bezerra
- Laboratório de Bioquímica Nutricional e de Alimentos, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil 21941-909
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21
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Rodríguez-Bores L, Fonseca GC, Villeda MA, Yamamoto-Furusho JK. Novel genetic markers in inflammatory bowel disease. World J Gastroenterol 2007; 13:5560-70. [PMID: 17948929 PMCID: PMC4172734 DOI: 10.3748/wjg.v13.i42.5560] [Citation(s) in RCA: 42] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Genetic factors play a significant role in determining inflammatory bowel disease (IBD) susceptibility. Epidemiologic data support genetic contribution to the pathogenesis of IBD, which include familial aggregation, twin studies, racial and ethnic differences in disease prevalence. Linkage studies have identified several susceptibility genes contained in different genomic regions named IBD1 to IBD9. Nucleotide oligomerization domain (NOD2) and human leukocyte antigen (HLA) genes are the most extensively studied genetic regions (IBD1 and IBD3 respectively) in IBD. Mutations of the NOD2 gene are associated with Crohn's disease (CD) and several HLA genes are associated with ulcerative colitis (UC) and CD. Toll like receptors (TLRs) have an important role in the innate immune response against infections by mediating recognition of pathogen-associated microbial patterns. Studying single-nucleotide polymorphisms (SNPs) in molecules involved in bacterial recognition seems to be essential to define genetic backgrounds at risk of IBD. Recently, numerous new genes have been identified to be involved in the genetic susceptibility to IBD: NOD1/Caspase-activation recruitment domains 4 (CARD4), Chemokine ligand 20 (CCL20), IL-11, and IL-18 among others. The characterization of these novel genes potentially will lead to the identification of therapeutic agents and clinical assessment of phenotype and prognosis in patients with IBD.
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22
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Cashman KD, Seamans K. Bone health, genetics, and personalised nutrition. GENES & NUTRITION 2007; 2:47-51. [PMID: 18850139 PMCID: PMC2474936 DOI: 10.1007/s12263-007-0010-0] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- Kevin D Cashman
- Department of Food and Nutritional Sciences, University College, Cork, Ireland,
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23
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Schaafsma A, van Doormaal JJ, Muskiet FAJ, Hofstede GJH, Pakan I, van der Veer E. Positive effects of a chicken eggshell powder-enriched vitamin–mineral supplement on femoral neck bone mineral density in healthy late post-menopausal Dutch women. Br J Nutr 2007. [DOI: 10.1079/bjn2001515] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Abstract
Although bone metabolism is largely under genetic control, the role of nutrition is considerable. The present study evaluates the effects of chicken eggshell powder, a new source of dietary Ca, and purified CaCO3 on bone mineral density (BMD) of the lumbar spine and hip. Besides BMD we also looked at biochemical markers of bone and Ca metabolism. Both Ca sources were provided in combination with minerals and vitamins including Mg, cholecalciferol and phylloquinone. We designed a randomised, double-blind, placebo-controlled study to take place over 12 months. Healthy Caucasian women (n 85), selected by age (≥50 and <70 years), from the databases of general practitioners were recruited by telephone calls. They had to be at least 5 years post-menopausal, with lumbar spine T-score being >-2·5. At baseline, their mean habitual daily Ca intake was adequate. The women were randomly allocated to: eggshell powder-enriched (group A; n 24), purified CaCO3-enriched (group B; n 22), or a placebo product (group C; n 27). BMD was measured at baseline and then after 6 and 12 months of supplementation as were the biochemical markers bone-specific alkaline phosphatase, amino-terminal propeptide extension of type I collagen, deoxypyridinoline, calcitonin, intact parathyroid hormone, calcidiol, and urinary Ca. After 12 months of supplementation, only mean BMD of the femoral neck in group A was significantly increased (P=0·014) by 1·75 % (95 % CI 0·18, 3·32) compared with a decrease of -0·60 % (95 % CI -1·92, 0·72) in group C. This increase coincided with significant decreases in markers of bone resorption and formation. No significant changes were seen in BMD at other sites, including lumbar spine, nor in groups B and C. No differences were found between groups A and B, or B and C. The present study indicates that healthy late post-menopausal women with an adequate Ca intake at baseline may increase BMD of the hip within 12 months following supplementation with the chicken eggshell powder-enriched supplement.
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Abstract
There is compelling evidence to suggest that both the development of bone to peak bone mass at maturity and subsequent loss depend on the interaction between genetic, hormonal, environmental and nutritional factors. The major part (≤80%) of the age-specific variation in bone turnover and bone density is genetically determined. However, the notion of genetic determinant is of little value unless the specific genes that are involved can be identified. Most work in this area of osteoporosis research has focused on the candidate gene approach, which has identified several candidate genes for osteoporosis, including genes encoding the vitamin D receptor (VDR), oestrogen receptors (α and β), apolipoprotein E, collagen type I α 1 and methylenetetrahydrofolate reductase, amongst many others. However, in general, findings from numerous studies of the association between such genes and various bone variables have been inconsistent. In addition to possible gene—gene interactions it is likely that there are interactions between these genes and certain environmental factors, especially nutrition, that may mediate expression of bone-related phenotypes. While these potential interactions add a level of complexity to our understanding of these apparent genetic effects on bone, identification of a role for genetic factors without knowledge of their interaction with nutrients can do little to advance prevention and treatment of osteoporosis. This information is especially important because, unlike genotype, diet and nutrition can be modified. The aim of the present review is to critically evaluate current knowledge relating to candidate genes for osteoporosis, with particular emphasis on their interaction with nutrients and dietary factors in determining bone health.
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Affiliation(s)
- Siobhán Cusack
- Department of Food and Nutritional Sciences, University College, Cork, Republic of Ireland
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25
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Rapuri PB, Gallagher JC, Nawaz Z. Caffeine decreases vitamin D receptor protein expression and 1,25(OH)2D3 stimulated alkaline phosphatase activity in human osteoblast cells. J Steroid Biochem Mol Biol 2007; 103:368-71. [PMID: 17223552 DOI: 10.1016/j.jsbmb.2006.12.037] [Citation(s) in RCA: 51] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/30/2006] [Indexed: 11/24/2022]
Abstract
Of the various risk factors contributing to osteoporosis, dietary/lifestyle factors are important. In a clinical study we reported that women with caffeine intakes >300 mg/day had higher bone loss and women with vitamin D receptor (VDR) variant, tt were at a greater risk for this deleterious effect of caffeine. However, the mechanism of how caffeine effects bone metabolism is not clear. 1,25-Dihydroxy vitamin D(3) (1,25(OH)(2)D(3)) plays a critical role in regulating bone metabolism. The receptor for 1,25(OH)(2)D(3), VDR has been demonstrated in osteoblast cells and it belongs to the superfamily of nuclear hormone receptors. To understand the molecular mechanism of the role of caffeine in relation to bone, we tested the effect of caffeine on VDR expression and 1,25(OH)(2)D(3) mediated actions in bone. We therefore examined the effect of different doses of caffeine (0.2, 0.5, 1.0 and 10mM) on 1,25(OH)(2)D(3) induced VDR protein expression in human osteoblast cells. We also tested the effect of different doses of caffeine on 1,25(OH)(2)D(3) induced alkaline phosphatase (ALP) activity, a widely used marker of osteoblastic activity. Caffeine dose dependently decreased the 1,25(OH)(2)D(3) induced VDR expression and at concentrations of 1 and 10mM, VDR expression was decreased by about 50-70%, respectively. In addition, the 1,25(OH)(2)D(3) induced alkaline phosphatase activity was also reduced at similar doses thus affecting the osteoblastic function. The basal ALP activity was not affected with increasing doses of caffeine. Overall, our results suggest that caffeine affects 1,25(OH)(2)D(3) stimulated VDR protein expression and 1,25(OH)(2)D(3) mediated actions in human osteoblast cells.
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Affiliation(s)
- Prema B Rapuri
- Bone Metabolism Unit, Creighton University, School of Medicine, 601 North 30th Street, Omaha, NE 68131, USA.
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Abstract
Osteoporosis is a significant public health issue in the United States. This common and costly disease is a major cause of disability in elderly women. Although advances have been made in awareness, prevention, diagnosis, and treatment, osteoporosis remains a silent and underdiagnosed disease for many women. However, osteoporosis is particularly underdiagnosed in women in racial and ethnic minority groups in the United States. Even though the opportunity for prevention is great, disparities in incidence, awareness, diagnosis, treatment, and outcomes exist across racial and ethnic lines.
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Affiliation(s)
- Patricia A Thomas
- Department of Pathology and Laboratory Medicine, University of Kansas School of Medicine, Kansas City, USA
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Abstract
A constant extracellular Ca2+ concentration is required for numerous physiological functions at tissue and cellular levels. This suggests that minor changes in Ca2+ will be corrected by appropriate homeostatic systems. The system regulating Ca2+ homeostasis involves several organs and hormones. The former are mainly the kidneys, skeleton, intestine and the parathyroid glands. The latter comprise, amongst others, the parathyroid hormone, vitamin D and calcitonin. Progress has recently been made in the identification and characterisation of Ca2+ transport proteins CaT1 and ECaC and this has provided new insights into the molecular mechanisms of Ca2+ transport in cells. The G-protein coupled calcium-sensing receptor, responsible for the exquisite ability of the parathyroid gland to respond to small changes in serum Ca2+ concentration was discovered about a decade ago. Research has focussed on the molecular mechanisms determining the serum levels of 1,25(OH)2D3, and on the transcriptional activity of the vitamin D receptor. The aim of recent work has been to elucidate the mechanisms and the intracellular signalling pathways by which parathyroid hormone, vitamin D and calcitonin affect Ca2+ homeostasis. This article summarises recent advances in the understanding and the molecular basis of physiological Ca2+ homeostasis.
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Affiliation(s)
- Indra Ramasamy
- Department of Chemical Pathology, Newham University Hospital, London, UK.
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28
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Cusack S, Mølgaard C, Michaelsen KF, Jakobsen J, Lamberg-Allardt CJE, Cashman KD. Vitamin D and estrogen receptor-alpha genotype and indices of bone mass and bone turnover in Danish girls. J Bone Miner Metab 2006; 24:329-36. [PMID: 16816928 DOI: 10.1007/s00774-006-0691-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2005] [Accepted: 01/23/2006] [Indexed: 10/24/2022]
Abstract
Peak bone mass is a major determinant of osteoporosis risk in later life. It is under strong genetic control; however, little is known about the identity of the genes involved. In the present study, we investigated the relationship between polymorphisms in the genes encoding the vitamin D receptor (VDR) (FokI, TaqI) and estrogen receptor-alpha (ERalpha) (PvuII, XbaI), and bone mineral density (BMD), bone mineral content (BMC), and markers of bone turnover in 224 Danish girls aged 11-12 years. BMD and BMC were measured by dual-energy X-ray absorptiometry. Serum osteocalcin, 25(OH)D, and parathyroid hormone (PTH) were measured by ELISA assays and urinary pyridinium cross-links by HPLC. Physical activity, dietary calcium, and Tanner stage were assessed by questionnaire. In general, there were no significant differences in anthropometrical variables, physical activity, dietary calcium, serum 25(OH)D, or PTH among genotype groups. BMD or BMC of lumbar spine or whole body (adjusted for body and bone size and pubertal status) were not associated with VDR or ERalpha genotypes or the combination of these genotypes. This lack of association remained even after adjustment for dietary and environmental factors. VDR genotypes had no effect on bone turnover markers. XX and PP ERalpha genotypes were associated (P < 0.05) with reduced levels of urinary pyridinium cross-links, whereas serum osteocalcin was similar among genotypes. These findings suggest that the rate of bone resorption was influenced by ERalpha genotypes, even though these biochemical differences were not evident in bone mass indices.
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Affiliation(s)
- Siobhan Cusack
- Department of Food and Nutritional Sciences, University College, Cork, Ireland
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29
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Kidd LCR, Paltoo DN, Wang S, Chen W, Akereyeni F, Isaacs W, Ahaghotu C, Kittles R. Sequence variation within the 5' regulatory regions of the vitamin D binding protein and receptor genes and prostate cancer risk. Prostate 2005; 64:272-82. [PMID: 15717311 DOI: 10.1002/pros.20204] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The vitamin D receptor (VDR) and binding protein (DBP) mediate the cellular transport, activity, and anti-tumor action of 1,25-dihydroxyvitamin D3 [1,25-(OH)(2)D3]. The purpose of this investigation is to determine whether novel single nucleotide polymorphisms (SNPs) within the transcriptional regulatory regions of the VDR and DBP are associated with prostate cancer risk. METHODS Novel SNPs were identified in the VDR and DBP transcription regulatory gene regions and genotyped in a case-control study using male subjects with (n=258) or without (n=434) prostate cancer. RESULTS African-American men who possessed at least one variant VDR-5132 C allele had a increased risk of prostate cancer (OR=1.83; 95% CI: 1.02, 3.31). Further study revealed that the VDR-5132 T/C SNP eliminates a GATA-1 transcription factor-binding site. CONCLUSION The VDR-5132 T/C SNP, resulting in potential elimination of the GATA-1 transcription factor-binding site, may increase prostate cancer susceptibility in African-Americans. Confirmation of these findings is needed in larger observational studies.
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Affiliation(s)
- La Creis R Kidd
- Department of Pharmacology and Toxicology, Cancer Prevention and Control Program, James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky
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30
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Rapuri PB, Gallagher JC, Knezetic JA, Kinyamu HK, Ryschon KL. Association between Vitamin D receptor polymorphisms and the rate of bone loss in elderly women-importance of adjusting for dietary and lifestyle factors. J Steroid Biochem Mol Biol 2004; 89-90:503-6. [PMID: 15225828 DOI: 10.1016/j.jsbmb.2004.03.060] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
The association between the restriction length polymorphisms of the Vitamin D receptor (VDR) gene and the bone mineral density (BMD) or the rate of bone loss is still under debate. In a longitudinal study of untreated postmenopausal elderly women, we evaluated the relationship between the VDR gene polymorphisms (BsmI, TaqI, ApaI, and FokI) and the rate of bone loss over a 3-year period. We also examined the effect of adjustments for dietary and lifestyle factors on these associations. Before adjustments, the rate of femoral neck bone loss was - 3.76 +/- 1.58% in women with BB genotype and 0.45 +/- 0.65% in women with bb genotype, which was not significantly different. Upon adjustment for dietary and lifestyle factors, statistically significant (P = 0.03) bone loss was observed at femoral neck in women with BB genotype (- 3.66 +/- 2.44%) compared to that of bb genotype (2.39 +/- 1.32%). Similar results were observed with TaqI genotypes. The rates of bone loss at other skeletal sites were not different between VDR genotypes defined by BsmI and TaqI. VDR gene polymorphisms defined by ApaI and FokI were not related to the rate of bone loss.
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Affiliation(s)
- P B Rapuri
- Bone Metabolism Unit, School of Medicine, Creighton University, Room 6718, 601 North 30th Street, Omaha, NE 68131, USA.
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Seko M, Takeuchi H, Kinoshita K, Tokita A. Association of bone mineral density with vitamin D and estrogen receptor gene polymorphisms during GnRH agonist treatment. J Obstet Gynaecol Res 2004; 30:130-5. [PMID: 15009617 DOI: 10.1111/j.1447-0756.2003.00172.x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
AIMS This study examined whether or not a decrease in bone mineral density (BMD) induced by the use of gonadotropin-releasing hormone agonist (GnRHa) during sexual maturation is affected by vitamin D receptor and/or estrogen receptor gene polymorphisms, like the phenomenon observed during the postmenopausal period. METHODS In 43 patients who received GnRHa therapy for 6 months to treat uterine myoma or endometriosis at our department and who were confirmed to have pituitary down-regulation, we measured bone density before and after GnRHa treatment using DXA and analyzed the bone metabolism turnover using bone metabolic markers. Polymorphisms were analyzed by RFLP using FokI and TaqI for the vitamin D receptor gene and PvuII and XbaI for the estrogen receptor gene. The then determined gene polymorphism was analyzed in relation to the percentage decreases in BMD following GnRHa treatment. RESULTS The patients were divided by f, t into two groups: (f, t) < 2 (Group V-I) and (f, t) > or = 2 (Group V-II). They were also divided by P, x into two groups (P, x) < 3 (Group E-I) and (P, x) > or = 3 (Group E-II). The BMD change was significantly higher in Group V-II than in Group V-I. Group E-II tended to have a higher BMD change than Group E-I, although this difference was not statistically significant. CONCLUSION Patients who often have f and t polymorphism are more likely to show BMD reduction following GnRHa therapy, like the phenomenon seen during the postmenopausal period, than patients with other gene polymorphisms. Measures to avoid BMD reduction are required when using GnRHa in such patients.
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Affiliation(s)
- Masami Seko
- Department of Obstetrics and Gynecology, Juntendo University School of Medicine, Tokyo, Japan.
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32
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Setchell KDR, Lydeking-Olsen E. Dietary phytoestrogens and their effect on bone: evidence from in vitro and in vivo, human observational, and dietary intervention studies. Am J Clin Nutr 2003; 78:593S-609S. [PMID: 12936954 DOI: 10.1093/ajcn/78.3.593s] [Citation(s) in RCA: 235] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023] Open
Abstract
Impressive data from the many studies on cultured bone cells and rat models of postmenopausal osteoporosis support a significant bone-sparing effect of the soy isoflavones genistein and daidzein. Translating this research to the clinic has been more challenging, and thus far only a few clinical studies have attempted to tease out the influence of phytoestrogens on bone from the many other components of the diet. Human studies have shown promising although variable results. Studies have been mostly of short duration and with relatively small sample sizes, making it difficult to observe significant and accurate changes in bone. Levels of intake of the soy protein and isoflavones are varied, and the optimal isoflavone intake for bone-sparing effects remains to be determined. Clinical studies thus far performed can be broadly divided into those that have assessed biochemical evidence of reduced bone turnover from measurement of surrogate markers of osteoblast and osteoclast activity, and those that have examined changes in bone mineral density. There are no studies examining effects on fracture rate. This review focuses specifically on the potential influence of phytoestrogens on bone by examining the evidence from 17 in vitro studies of cultured bone cells, 24 in vivo studies of animal models for postmenopausal osteoporosis, 15 human observational/epidemiologic studies, and 17 dietary intervention studies. On balance, the collective data suggest that diets rich in phytoestrogens have bone-sparing effects in the long term, although the magnitude of the effect and the exact mechanism(s) of action are presently elusive or speculative.
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Affiliation(s)
- Kenneth D R Setchell
- Department of Pediatrics, Clinical Mass Spectrometry, Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
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Froes NDTC, Pereira EDS, Negrelli WF. Fatores de risco da osteoporose: prevenção e detecção através do monitoramento clínico e genético. ACTA ORTOPEDICA BRASILEIRA 2002. [DOI: 10.1590/s1413-78522002000100007] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
A osteoporose é uma doença sistêmica caracterizada pela baixa massa óssea e deterioração da micro arquitetura do tecido ósseo. Consequentemente existe um aumento na fragilidade do osso e suscetibilidade à fratura, que é considerada o efeito clínico mais importante deste processo. Muitos estudos que se utilizam de modelos em gêmeos ou pais e seus descendentes têm confirmado o papel da herança genética no pico de massa óssea, na verdade o maior fator de risco da fratura. Neste artigo de revisão, são enfocados os prováveis genes envolvidos no processo de osteoporose, ressaltando a importância das interações entre gene- gene e gene-ambiente. Concernente à influência isolada do ambiente, são abordados os hábitos relacionados ao estilo de vida, à nutrição e ao tabagismo envolvidos no aparecimento dessa doença. Durante os próximos anos, o conhecimento baseado na genética molecular elucidará o processo osteoporótico. Do mesmo modo, os estudos clínicos se expandirão, visando contribuir para a detecção precoce da doença, permitindo assim a aplicação de medidas preventivas e terapêuticas adequadas.
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Heilberg IP, Teixeira SH, Martini LA, Boim MA. Vitamin D receptor gene polymorphism and bone mineral density in hypercalciuric calcium-stone-forming patients. Nephron Clin Pract 2002; 90:51-7. [PMID: 11744805 DOI: 10.1159/000046314] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
Reduced bone mineral density (BMD) and an increased risk of vertebral fracture have been reported in calcium-stone-forming (CSF) patients presenting with idiopathic hypercalciuria. We investigated the association between BsmI vitamin D receptor (VDR) polymorphism and BMD in 68 hypercalciuric CSF patients (35 males and 33 premenopausal females, mean age +/- SD = 39 +/- 10 years). BMD was measured at lumbar spine (L2-L4) and femur neck sites using dual energy X-ray absorptiometry. A 72-hour dietary record and a 24-hour urine sample were obtained from each patient to determine calcium intake and excretion. The allelic frequency found for the sample as a whole was 16% BB, 44% Bb and 40% bb. Mean BMD values did not significantly differ among BB, Bb and bb patients at L2-L4 (1.162 +/- 0.10, 1.133 +/- 0.11 and 1.194 +/- 0.19 g/cm2, mean +/- SD, respectively) or at neck sites (0.920 +/- 0.11, 0.931 +/- 0.15 and 0.982 +/- 0.15 g/cm2, respectively). Calcium intake and excretion were also not significantly different among the three genotypes. Patients were then divided into two groups, normal BMD, T-score > or =-1 (n = 34) and low BMD, T-score <-1 (n = 34), to further evaluate the allele influence on previous bone loss. Despite a trend for a higher mean BMD at spine or neck sites for patients with one or two b alleles when compared to BB patients, the difference did not reach statistical significance. The distribution of BB, Bb and bb genotypes in the low-bone-mass group (15, 47 and 38%, respectively) was similar to that in the normal-bone-mass group (18, 41 and 14%, respectively). These data suggest that BsmI VDR polymorphism does not play an important role in the bone loss seen in hypercalciuric CSF patients.
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Affiliation(s)
- Ita Pfeferman Heilberg
- Nephrology Division, Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, Brazil.
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Abstract
Two recent studies suggest that when consuming a low-calcium diet, low efficiency of calcium absorption (measured as fractional calcium absorption) is a problem in the elderly; this is also an important risk factor for hip fracture. These studies show that elderly women are less able to compensate for low calcium intake by increasing calcium absorption and that within that age group, those who are least able to adapt are more likely to experience hip fractures. A novel explanation for this phenomenon is that a genetic predisposition for low calcium absorption efficiency exists that can be alleviated by a simple dietary change--improved calcium intake.
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Affiliation(s)
- J Fleet
- Department of Foods and Nutrition, Purdue University, West Lafayette, IN 47906, USA
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36
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Whitfield GK, Remus LS, Jurutka PW, Zitzer H, Oza AK, Dang HT, Haussler CA, Galligan MA, Thatcher ML, Encinas Dominguez C, Haussler MR. Functionally relevant polymorphisms in the human nuclear vitamin D receptor gene. Mol Cell Endocrinol 2001; 177:145-59. [PMID: 11377830 DOI: 10.1016/s0303-7207(01)00406-3] [Citation(s) in RCA: 305] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
The functional significance of two unlinked human vitamin D receptor (hVDR) gene polymorphisms was evaluated in twenty human fibroblast cell lines. Genotypes at both a Fok I restriction site (F/f) in exon II and a singlet (A) repeat in exon IX (L/S) were determined, and relative transcription activities of endogenous hVDR proteins were measured using a transfected, 1,25-dihydroxyvitamin D(3)-responsive reporter gene. Observed activities ranged from 2--100-fold induction by hormone, with higher activity being displayed by the F and the L biallelic forms. Only when genotypes at both sites were considered simultaneously did statistically significant differences emerge. Moreover, the correlation between hVDR activity and genotype segregated further into clearly defined high and low activity groups with similar genotypic distributions. These results not only demonstrate functional relevance for both the F/f and L/S common polymorphisms in hVDR, but also provide novel evidence for a third genetic variable impacting receptor potency.
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Affiliation(s)
- G K Whitfield
- Department of Biochemistry, College of Medicine, 1501 N. Campbell Ave., University of Arizona, Tucson, AZ 85724, USA
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Abstract
Osteoporosis affects approximately 10 million Americans; of these, 2 million are men. An estimated 3.5 million additional men are at risk of developing the disease. Individuals with osteoporosis commonly incur fractures of the spine, hip, and forearm. The clinical spectrum of osteoporosis is similar in men and women; however, differences exist in skeletal development, age-related bone loss, modifiable and nonmodifiable risk factors, and secondary causes. Prevention and early detection is achieved through identification of risk factors and secondary causes. Treatment options include risk factor reduction, correction of underlying disease, and use of pharmacologic and nonpharmacologic therapies.
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Affiliation(s)
- M T Lawson
- College of Nursing and Health Professions, University of Southern Maine, Portland, USA
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38
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Sheehan D, Bennett T, Cashman KD. An assessment of genetic markers as predictors of bone turnover in healthy adults. J Endocrinol Invest 2001; 24:236-45. [PMID: 11383910 DOI: 10.1007/bf03343853] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
In 1992 a significant relationship between bone turnover and the vitamin D receptor (VDR) genotype was reported in Australian subjects of UK-Irish decent. Since then, several groups have investigated the relationship between VDR and other bone-related genotypes, bone mass and bone turnover in several populations. However, the results of these studies are conflicting. Therefore, our aim was to determine bone-related genotypes in a population of healthy Irish adults and relate these genotypes to the rate of bone turnover. One hundred and eighteen healthy Irish adults (aged 19-67 yr) were recruited and fasting blood and first void urines were collected from each subject. Bone-related genotype frequencies in healthy Irish adults were similar to those reported in other Caucasian populations and were in Hardy-Weinberg equilibrium. Estrogen receptor (Pvu II or Xba I), apolipoprotein E and collagen IA1 genotypes were not related to bone turnover. The tt VDR genotype was associated with significantly higher serum osteocalcin (29% and 40%) compared with the Tt and TT genotypes, respectively. The ff VDR genotype was associated with significantly higher urinary pyridinoline (by approximately 44% and approximately 29%) and deoxypyridinoline (by approximately 76% and approximately 58%) levels and higher serum osteocalcin (by approximately 25% and approximately 53%) compared with the Ff or FF genotypes, respectively. These findings suggest that healthy Irish adults with either the tt or ff VDR genotype have higher rates of bone turnover than those with Tt or TT, or Ff or FF genotypes, respectively, and therefore may have a higher risk of low bone mineral density and osteoporosis in later life.
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Affiliation(s)
- D Sheehan
- Department of Nutrition, University College, Cork, Ireland
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39
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Videman T, Gibbons LE, Battié MC, Maravilla K, Vanninen E, Leppävuori J, Kaprio J, Peltonen L. The relative roles of intragenic polymorphisms of the vitamin d receptor gene in lumbar spine degeneration and bone density. Spine (Phila Pa 1976) 2001; 26:E7-E12. [PMID: 11224872 DOI: 10.1097/00007632-200102010-00003] [Citation(s) in RCA: 93] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
STUDY DESIGN A retrospective cohort study. OBJECTIVES To compare the magnitudes of the associations of TaqI polymorphisms of the vitamin D receptor gene with bone density and lumbar spine degeneration in the same sample. SUMMARY OF BACKGROUND DATA Vitamin D receptor gene variations are associated with osteoporosis, osteoarthritis, and disc degeneration. Their role in these conditions remains poorly understood. METHODS Bone density of the spine and femur were determined through DEXA, and lumbar disc degeneration was determined from magnetic resonance imaging assessments of signal intensity, disc narrowing, bulging, anular tears, herniations, and osteophytes. Associations between these measures and TaqI polymorphisms of the coding region of the Vitamin D receptor locus were examined in a population-based sample of 142 men. RESULTS The strongest associations were with signal intensity and anular tears, which were worse for the subjects with tt genotypes than for those with TT genotypes in the L4-S1 spine discs. Conversely, the prevalences of disc bulges and osteophytes were lowest for the tt genotype. Bone density, disc height, and herniations did not differ significantly by genotype. CONCLUSIONS The strongest association of Vitamin D receptor TaqI polymorphisms with degeneration in nonmineralized connective tissues suggests that the underlying mechanism of TaqI polymorphisms is not specific to bone. This study demonstrated for the first time that those with the tt genotype had more anular tears than those with the TT genotype, a finding that should stimulate further analyses of this gene in conditions that result in back pain. The apparent discrepancies of the associations of the tt genotype with lower signal intensity and more anular tears, but less bulges and osteophytes, could be explained if bulging and osteophytes primarily represented remodeling related to lifetime physical loading.
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Affiliation(s)
- T Videman
- Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland.
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40
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Sheehan D, Bennett T, Cashman K. The genetics of osteoporosis: vitamin D receptor gene polymorphisms and circulating osteocalcin in healthy Irish adults. Ir J Med Sci 2001; 170:54-7. [PMID: 11440415 DOI: 10.1007/bf03167723] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND A relationship between bone turnover and the vitamin D receptor (VDR) genotype is reported in Australian subjects of UK-Irish descent. There is conflicting evidence of linkage between the VDR genotype and differences in bone mineral density. No such study has been carried out on a resident Irish population. AIMS This study examined the relationship between serum osteocalcin (a marker of bone turnover) and VDR genotype in Irish adults. METHODS One hundred and eighteen healthy Irish adults aged between 19 and 67 were recruited and had two fasting blood samples taken. One sample was analysed for osteocalcin by enzyme immunoassay. The other was used to isolate genomic DNA and determine VDR genotype. RESULTS Tt was the most prevalent VDR genotype (53%) and tt (15%) the least prevalent in this group of healthy Irish adults. The tt VDR genotype was associated with significantly higher levels of serum osteocalcin (29% and 40%) than the Tt or TT VDR genotypes. CONCLUSIONS These findings suggest that healthy Irish adults with the tt VDR genotype have higher rates of bone turnover than those with Tt or TTVDR genotypes. They may have a higher risk of low bone mineral density and osteoporosis in later life.
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Affiliation(s)
- D Sheehan
- Department of Nutrition, University College Cork, Ireland
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Tanaka A, Borchers AT, Ishibashi H, Ansari AA, Keen CL, Gershwin ME. Genetic and familial considerations of primary biliary cirrhosis. Am J Gastroenterol 2001; 96:8-15. [PMID: 11197292 DOI: 10.1111/j.1572-0241.2001.03446.x] [Citation(s) in RCA: 47] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The genetic basis of human autoimmune diseases is receiving increasing attention. Primary biliary cirrhosis (PBC) is a model autoimmune disease reflective of other organ-specific autoimmune pathology. PBC is an enigmatic autoimmune disease that predominantly affects women and leads to destruction of intrahepatic bile ducts. The serological hallmark of this disease is characterized by antimitochondrial antibodies that specifically react with the E2 components of 2-oxodehydrogenase enzymes, including PDC-E2. There are no clear major histocompatibility complex associations with the development of PBC, despite the observation that first-degree relations of index patients with PBC have a 4-6% prevalence of development of PBC. This risk factor is comparable or higher than any other human autoimmune disease and suggests that a genome-wide approach towards dissection of genetic associations would lead to valuable new insights. In this review, we place these concepts in perspective and highlight in particular the genetic associations in PBC and the importance of studying siblings with PBC who are concordant for disease.
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Affiliation(s)
- A Tanaka
- The Institute for Adult Diseases, Asahi Life Foundation, Tokyo, Japan
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43
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Abstract
Bone ageing results from a complex interaction between genetic and environmental factors (such as diet, climate and physical exercise) throughout human life. According to current literature, the most popular measures of bone ageing are osseometric measurements (OSM), bone mineral density (BMD) and osseographic scores (OSS), based on descriptive criteria of bone age. Plain roentgenography allows simultaneous assessment of all three measures. Ethnic differences with regard to these bone ageing characteristics have prompted us to study to the process anew, with the aim of elucidation the nature of the genetic and environmental components involved, and the possible interaction(s) between them. Despite abundant data on ethnic differences regarding these measures, modern knowledge on the genetics of these processes has derived primarily from the family studies of BMD, which pointed to strong involvement of the familial factors on bone mass. Segregation analysis performed by us in two ethnically different samples of pedigrees revealed a significant effect of the putative major gene on BMD of both compact and cancellous bone. The major finding of our bivariate segregation analysis was that it lead to the acceptance of the hypothesis predicating a single major locus with pleiotropy to both cancellous and compact BMD, but clearly rejecting the polygenic hypotheses. Our study of cortical index (CI) provided evidence that a single potential major gene controls not only the baseline trait level, but also the age at onset of the involutive bone changes, and the rate of the CI change with age. When we examined the environmental vs genetic influences on OSS variation in 32 human populations, we found very little environmental effect on the rate of bone change (r2 = 0.107), but a substantial effect on this rate of the genetic differences between populations (r = 0.480). Clarification of the genetic basis of bone ageing could have wide-ranging applications in the prevention and treatment of bone degenerative diseases such as osteoporosis and osteoarthritis, before irreversible damage takes place. There is thus a need to target the genetic analysis of BMD and the biochemical regulating factors of bone turnover through the use of molecular genetic techniques.
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Affiliation(s)
- E Kobyliansky
- Department of Anatomy and Anthropology, Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
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44
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Lutz W, Burritt MF, Nixon DE, Kao PC, Kumar R. Zinc increases the activity of vitamin D-dependent promoters in osteoblasts. Biochem Biophys Res Commun 2000; 271:1-7. [PMID: 10777672 DOI: 10.1006/bbrc.2000.2570] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Zinc modulates the structure and binding of the DNA binding domain of the 1alpha,25-dihydroxyvitamin D(3) receptor to specific vitamin D response element DNA (Nature Biotechnology 16, 262-266, 1998). To determine whether zinc alters 1alpha,25-dihydroxyvitamin D(3)-regulated genes in cells, we permanently transfected rat osteoblasts with two vitamin D-dependent promoter-reporter systems and examined their responses to 1alpha,25-dihydroxyvitamin D(3) in the presence of increasing amounts of extracellular zinc. When extracellular zinc concentrations were increased in the presence of 1alpha,25-dihydroxyvitamin D(3), there was an increase in the activity of 1alpha,25-dihydroxyvitamin D(3)-dependent promoters with increasing concentrations of zinc. The effect was specific for zinc since metals such as copper failed to increase the activity of 1alpha,25-dihydroxyvitamin D(3)-dependent promoters. The concentration of the vitamin D receptor within the cell and the affinity of 1alpha,25-dihydroxyvitamin D(3) for its receptor remained unchanged with added zinc. Our results show that zinc increases the activity of 1alpha,25-dihydroxyvitamin D(3)-dependent promoters in osteoblasts.
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Affiliation(s)
- W Lutz
- Nephrology Research Unit, Mayo Clinic and Foundation, 200 First Street SW, Rochester, Minnesota, 55905, USA
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45
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Lorentzon M, Lorentzon R, Nordström P. Vitamin D receptor gene polymorphism is associated with birth height, growth to adolescence, and adult stature in healthy caucasian men: a cross-sectional and longitudinal study. J Clin Endocrinol Metab 2000; 85:1666-70. [PMID: 10770213 DOI: 10.1210/jcem.85.4.6566] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Vitamin D receptor (VDR) polymorphism has been associated with bone mineral density (BMD), but recent data indicate association to parameters of body constitution and growth. We investigated VDR gene polymorphism, defined by BsmI and TaqI, in 90 healthy Caucasian males and any relation with parameters of body constitution at birth, and to parameters of body constitution, BMD and bone area, at age 16.9 +/- 0.3 yr (mean +/- SD) and at age 19.2 +/- 0.7. Using PCR and the restriction enzyme BsmI and TaqI, the allelic variants BB, Bb, and bb, and TT, Tt, and tt were identified. Height (cm) and weight (kg) were measured using standardized equipment, and BMD of the total body, lumbar spine, and femoral neck, and bone area (cm2) of the total body, humerus, femur was measured using dual-energy x-ray absorptiometry. BsmI and TaqI genotypes were related in 89 of the 90 cases; hence, the same associations were found for both genotypes. Boys with the BB genotype were shorter at birth (P = 0.01) and grew less from birth to age 16.9 +/- 0.3 (P = 0.01) than their Bb and bb counterparts. Both during puberty (age 16.9 +/- 0.3) and after puberty (age 19.3 +/- 0.7), the BB boys were shorter (P = 0.005-0.008) and had lower bone area of the humerus, femur, and total body (P < 0.05) than the Bb and bb boys. The allelic variants were not related to BMD at any site. A prediction model including parental height, birth height, birth weight, and VDR alleles could predict up to 39% of the total variation in adult height in our population. The VDR allelic variants alone contributed to 8% of the total variation.
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Affiliation(s)
- M Lorentzon
- Sports Medicine, Department of Surgical and Perioperative Sciences, National Institute for Working Life, Umeå University, Sweden
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46
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Jurutka PW, Remus LS, Whitfield GK, Thompson PD, Hsieh JC, Zitzer H, Tavakkoli P, Galligan MA, Dang HT, Haussler CA, Haussler MR. The polymorphic N terminus in human vitamin D receptor isoforms influences transcriptional activity by modulating interaction with transcription factor IIB. Mol Endocrinol 2000; 14:401-20. [PMID: 10707958 DOI: 10.1210/mend.14.3.0435] [Citation(s) in RCA: 239] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022] Open
Abstract
The human vitamin D receptor (hVDR) is a ligand-regulated transcription factor that mediates the actions of the 1,25-dihydroxyvitamin D3 hormone to effect bone mineral homeostasis. Employing mutational analysis, we characterized Arg-18/Arg-22, hVDR residues immediately N-terminal of the first DNA binding zinc finger, as vital for contact with human basal transcription factor IIB (TFIIB). Alteration of either of these basic amino acids to alanine also compromised hVDR transcriptional activity. In contrast, an artificial hVDR truncation devoid of the first 12 residues displayed both enhanced interaction with TFIIB and transactivation. Similarly, a natural polymorphic variant of hVDR, termed F/M4 (missing a FokI restriction site), which lacks only the first three amino acids (including Glu-2), interacted more efficiently with TFIIB and also possessed elevated transcriptional activity compared with the full-length (f/M1) receptor. It is concluded that the functioning of positively charged Arg-18/Arg-22 as part of an hVDR docking site for TFIIB is influenced by the composition of the adjacent polymorphic N terminus. Increased transactivation by the F/M4 neomorphic hVDR is hypothesized to result from its demonstrated enhanced association with TFIIB. This proposal is supported by the observed conversion of f/M1 hVDR activity to that of F/M4 hVDR, either by overexpression of TFIIB or neutralization of the acidic Glu-2 by replacement with alanine in f/M1 hVDR. Because the f VDR genotype has been associated with lower bone mineral density in diverse populations, one factor contributing to a genetic predisposition to osteoporosis may be the F/f polymorphism that dictates VDR isoforms with differential TFIIB interaction.
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Affiliation(s)
- P W Jurutka
- Department of Biochemistry, College of Medicine, University of Arizona, Tuscon 85724, USA
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Cohen AJ, Roe FJ. Review of risk factors for osteoporosis with particular reference to a possible aetiological role of dietary salt. Food Chem Toxicol 2000; 38:237-53. [PMID: 10717363 DOI: 10.1016/s0278-6915(99)00145-3] [Citation(s) in RCA: 60] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Abstract
Laboratory animal, clinical and epidemiological studies in the published literature have been reviewed in order to establish whether excessive salt intake is an important risk factor for the development of osteoporosis and whether an intervention strategy based on salt restriction would be beneficial in the prevention of osteoporosis. Genetic factors appear to be far more important than the combination of nutritional, hormonal, environmental and lifestyle factors in the pathogenesis of osteoporosis. The most important single non-genetic factor is oestrogen deficiency in postmenopausal women. Preventive measures should be aimed at maximizing peak bone mass at skeletal maturity and retarding bone loss thereafter. Apart from postmenopausal oestrogen deficiency, various factors have been incriminated as risk factors for osteoporosis, and these include age at menarche, age at and years since menopause, insufficient physical exercise, alcohol, smoking, low calcium intake, low or high protein intake and high intake of phosphorus, sodium or caffeine. Many of the risk factors are considered to be weak, although when combined they could impact significantly on bone health. Increased intakes of various nutritional factors (potassium, magnesium, zinc, vitamin C), fibre and alkaline-producing fruit and vegetables favour adult bone health. Calcium homeostasis is normally well regulated such that increased calcium loss via the urine leads to increased calcium absorption from the gut. However, the duration of this adaptive process may be greater than that of many of the studies demonstrating that increased salt intake leads to both increased sodium and calcium in the urine. In any case, higher urinary calcium output appears to be seen only in a minority of humans in response to increased salt intake. As numerous factors-genetic, nutritional, hormonal and lifestyle-are involved in the maintenance of calcium homeostasis, it is difficult to devise human studies which adequately take into account all the important factors. Another difficulty is that many past studies have relied on imprecise methods for the measurement of bone resorption. Nor have studies based on the use of the laboratory rat produced clear answers to the problem because the rat, as a species, is uniquely deficient in its ability to handle the relevant minerals. Limited studies to date indicate that increased sodium intake neither exerts a consistent effect on various biomarkers of bone health nor leads to irreversible changes in the bone modelling process in men or in pre- or postmenopausal women. We conclude from the available evidence that increased sodium (or salt) intake is not an important risk factor for osteoporosis and that a reduction of salt intake from 9 to 6g/day in the diet would not be beneficial as an intervention measure in the prevention of osteoporosis. More research is needed to (i) assess the effects (especially long-term) of various nutrients including sodium on bone health, (ii) assess the long-term value of any intervention strategy involving reduced intake of a particular nutrient such as sodium; and (iii) determine whether subpopulations exist particularly in the elderly (e.g. sodium-responsive subjects) in which adaptation to sodium-induced hypercalciuria may be compromised. General prudence dictates that excessively high levels of dietary salt should be eschewed by those persons with raised blood pressure or a limited range of genetic disorders. However, for the generally healthy person there is no sound evidence that the consumption of salt at the present average level of 9g/day constitutes a risk factor for osteoporosis.
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Affiliation(s)
- A J Cohen
- Toxicology Advisory Services, Hamilton House, 17 Cedar Road, Sutton, Surrey, SM2 5DA, UK
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Audí L, García-Ramírez M, Carrascosa A. Genetic determinants of bone mass. HORMONE RESEARCH 1999; 51:105-23. [PMID: 10461016 DOI: 10.1159/000023343] [Citation(s) in RCA: 31] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
Abstract
A genetic contribution to bone mass determination was first described in the early 70s. Elucidation of gene contribution to this has since been attempted through studies analyzing associations between bone mass acquisition and/or maintenance and polymorphic variations of several genes. The first to be described was the vitamin D receptor gene (VDR), initially claimed to contribute to almost 75% of the genetic variation in bone mineral density (BMD) in twin and general population studies. Not all of the studies published to date conclude that a clear relationship exists between polymorphic VDR alleles and BMD, and the molecular basis for the VDR gene polymorphisms influence on bone mineralization has not yet been clarified. Since then, other genes with a significant role in bone metabolism such as estradiol receptor, collagen type 1alpha1, TGF-beta1, interleukin-6, calcitonin receptor, alpha2-HS-glycoprotein, osteocalcin, calcium-sensing receptor, interleukin-1 receptor antagonist, beta3-adrenergic receptor, apolipoprotein E, PTH, IGF-I and glucocorticoid receptor have been analyzed. Some polymorphic variations in these genes have been associated in some works with significant differences in BMD, with even more significant contributions when associations of different gene polymorphisms were analyzed. Again, the molecular basis for the contribution of these alleles to bone mass determination has not yet been described. A different approach has been attempted by linkage analysis of loci involved in bone density in pedigrees with low BMD using BMD as a quantitative trait. Recent results do not confirm, in these families, any association with any of the previously reported genes, but rather with other as yet unidentified genes. The genetic contribution to mild variations in the general population, as a result of environmental and endogenous individual influences, probably differs completely from that providing a pathologic BMD.
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Affiliation(s)
- L Audí
- Unidad de Investigaciones en Endocrinología y Nutrición Pediátricas, Hospital Materno-Infantil Valle de Hebrón, Universidad Autónoma de Barcelona, Spain.
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