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IL6 genetic variants haplotype is associated with susceptibility and disease activity but not with therapy response in patients with inflammatory bowel disease. Int J Colorectal Dis 2021; 36:383-393. [PMID: 33047210 DOI: 10.1007/s00384-020-03743-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/08/2020] [Indexed: 02/07/2023]
Abstract
PURPOSE The aim of the present study was to evaluate the IL6 -174 G>C (rs1800795) and -572 G>C (rs1800796) genetic variants and their association with inflammatory bowel diseases (IBDs), disease activity, and response to TNF-α inhibitors. METHODS The study included 178 patients with IBD and 224 healthy controls. Among the IBD patients, 66 of them were in use of TNF-α inhibitors therapy and were followed during 48 weeks and categorized as responders and non-responders. RESULTS In total, 89 (50.0%) had ulcerative colitis (UC) and 89 (50.0%) had Crohn's disease (CD). The IL6 -572 CC genotype presented a protective effect in CD patients in codominant and recessive models, while the IL6 -174 CC genotype was associated with susceptibility to UC and CD. The presence of G/C haplotype in the recessive model (GCGC) was associated with UC. The Crohn's disease endoscopic index of severity was low in those patients carrying the GCGC haplotype. It was observed that there was no association between the IL6 genetic variants and TNF-α inhibitor therapy response. CONCLUSION The G/C haplotype (recessive model) was associated with susceptibility to UC but not to CD. However, the G/C haplotype (dominant model) was associated with the endoscopic activity of CD. Moreover, these IL6 variants did not predict the TNF-α inhibitor therapy response.
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Mechanisms Underlying Bone Loss Associated with Gut Inflammation. Int J Mol Sci 2019; 20:ijms20246323. [PMID: 31847438 PMCID: PMC6940820 DOI: 10.3390/ijms20246323] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2019] [Revised: 11/29/2019] [Accepted: 12/10/2019] [Indexed: 12/11/2022] Open
Abstract
Patients with gastrointestinal diseases frequently suffer from skeletal abnormality, characterized by reduced bone mineral density, increased fracture risk, and/or joint inflammation. This pathological process is characterized by altered immune cell activity and elevated inflammatory cytokines in the bone marrow microenvironment due to disrupted gut immune response. Gastrointestinal disease is recognized as an immune malfunction driven by multiple factors, including cytokines and signaling molecules. However, the mechanism by which intestinal inflammation magnified by gut-residing actors stimulates bone loss remains to be elucidated. In this article, we discuss the main risk factors potentially contributing to intestinal disease-associated bone loss, and summarize current animal models, illustrating gut-bone axis to bridge the gap between intestinal inflammation and skeletal disease.
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Sgambato D, Gimigliano F, De Musis C, Moretti A, Toro G, Ferrante E, Miranda A, De Mauro D, Romano L, Iolascon G, Romano M. Bone alterations in inflammatory bowel diseases. World J Clin Cases 2019; 7:1908-1925. [PMID: 31423424 PMCID: PMC6695530 DOI: 10.12998/wjcc.v7.i15.1908] [Citation(s) in RCA: 39] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Revised: 06/14/2019] [Accepted: 06/26/2019] [Indexed: 02/05/2023] Open
Abstract
Inflammatory bowel diseases (IBDs) are characterized by a multifactorial partially unknown etiology that involves genetic, immunological and environmental factors. Up to 50% of IBD patients experience at least one extraintestinal manifestation; among them is the involvement of bone density which is referred to as metabolic bone disease (MBD), including osteopenia and osteoporosis. Bone alterations in IBDs population appear to have a multifactorial etiology: Decreased physical activity, inflammation-related bone resorption, multiple intestinal resections, dietary malabsorption of minerals and vitamin D deficiency, genetic factors, gut-bone immune signaling interaction, steroid treatment, microbiota and pathogenic micro-organisms interaction, and dietary malabsorption of minerals, that, all together or individually, may contribute to the alteration of bone mineral density. This review aims to summarize the prevalence and pathophysiology of metabolic bone alterations in IBD subjects outlining the main risk factors of bone fragility. We also want to underline the role of the screening and prophylaxis of bone alterations in Crohn's disease and ulcerative colitis patients and the importance of treating appropriately MBD.
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Affiliation(s)
- Dolores Sgambato
- Departments of Precision Medicine and Polyspecialistic Internal Medicine, University of Campania ‘‘Luigi Vanvitelli’’ and University Hospital, Naples 80131, Italy
| | - Francesca Gimigliano
- Department of Physical and Mental Health, University of Campania “Luigi Vanvitelli”, Naples 80131, Italy
| | - Cristiana De Musis
- Departments of Precision Medicine and Polyspecialistic Internal Medicine, University of Campania ‘‘Luigi Vanvitelli’’ and University Hospital, Naples 80131, Italy
| | - Antimo Moretti
- Department of Medical and Surgical Specialties and Dentistry, University of Campania “Luigi Vanvitelli”, Naples 80131, Italy
| | - Giuseppe Toro
- Department of Medical and Surgical Specialties and Dentistry, University of Campania “Luigi Vanvitelli”, Naples 80131, Italy
| | - Emanuele Ferrante
- Departments of Precision Medicine and Polyspecialistic Internal Medicine, University of Campania ‘‘Luigi Vanvitelli’’ and University Hospital, Naples 80131, Italy
| | - Agnese Miranda
- Departments of Precision Medicine and Polyspecialistic Internal Medicine, University of Campania ‘‘Luigi Vanvitelli’’ and University Hospital, Naples 80131, Italy
| | - Domenico De Mauro
- Departments of Precision Medicine and Polyspecialistic Internal Medicine, University of Campania ‘‘Luigi Vanvitelli’’ and University Hospital, Naples 80131, Italy
| | - Lorenzo Romano
- Surgical Digestive Endoscopy, Department of Clinical Medicine and Surgery, Federico II University, Naples 80131, Italy
| | - Giovanni Iolascon
- Department of Medical and Surgical Specialties and Dentistry, University of Campania “Luigi Vanvitelli”, Naples 80131, Italy
| | - Marco Romano
- Departments of Precision Medicine and Polyspecialistic Internal Medicine, University of Campania ‘‘Luigi Vanvitelli’’ and University Hospital, Naples 80131, Italy
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Wu J, Yu M, Zhou Y. Association of collagen type I alpha 1 +1245G/T polymorphism and osteoporosis risk in post-menopausal women: a meta-analysis. Int J Rheum Dis 2017; 20:903-910. [PMID: 28261929 DOI: 10.1111/1756-185x.13052] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
AIM To fully understand the association between collagen type I alpha 1 (COL1A1) +1245G/T polymorphism and osteoporosis risk in post-menopausal women. METHODS We searched the electronic databases including PubMed, Embase and Cochrane library updated to January 2016, as well as printed articles. Studies were screened according to the predefined inclusion and exclusion criteria, and the included studies were further assessed by Clark scores system. Furthermore, the association between COL1A1 +1245G/T polymorphism and osteoporosis risk was assessed using odds ratios (ORs) and their 95% confidence intervals (95% CIs). Additionally, the meta-analysis was carried out using Review Manger 5.1 software (Cochrane Collaboration, Oxford, UK) and Stata 11.0 software (StataCorp, College Station, TX, USA). RESULTS A total of five studies, which contained 1557 subjects (including 458 osteoporosis patients, 269 osteopenic patients and 830 normal controls), were included. Further, the included studies achieved Clark scores no less than 5, indicating a moderate or high quality. The pooled effect size indicated that there was a significant association between COL1A1 +1245G/T polymorphism and osteoporosis risk only under a co-dominant model (GG vs. TT, OR = 2.45, 95% CI = 1.11-5.44, P = 0.03). Moreover, there was no significant correlation between COL1A1 +1245G/T polymorphism and osteopenic risk under each model (P > 0.05). CONCLUSION There might be a certain relationship between GG genotype of COL1A1 +1245G/T polymorphism and osteoporosis risk in post-menopausal women.
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Affiliation(s)
- Jian Wu
- Department of Orthopaedic Surgery, Beijing Jishuitan Hospital, Fourth Clinical College of Peking University, Beijing, China
| | - Meng Yu
- Department of Orthopedics, Beijing Shijitan Hospital Affiliated to Capital Medical University, Beijing, China
| | - Yixin Zhou
- Department of Orthopaedic Surgery, Beijing Jishuitan Hospital, Fourth Clinical College of Peking University, Beijing, China
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Yao L, Wang H, Dong W, Liu Z, Mao H. Efficacy and safety of bisphosphonates in management of low bone density in inflammatory bowel disease: A meta-analysis. Medicine (Baltimore) 2017; 96:e5861. [PMID: 28099343 PMCID: PMC5279088 DOI: 10.1097/md.0000000000005861] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
This study aims to determine whether bisphosphonates are safe, as well as effective against bone mineral loss in inflammatory bowel disease (IBD). A computerized search of electronic databases from 1966 to 2016 was performed. Randomized controlled trials (RCTs) were included in this review to evaluate the role of bisphosphonates in the management of osteoporosis in IBD patients. A revised 7-point Jadad scale was used to evaluate the quality of each study. Overall, 13 RCTs and 923 patients met the inclusion criteria of this meta-analysis. The result showed that bisphosphonates decreased bone mass density (BMD) loss at the lumbar spine (P = 0.0002), reduced the risk of new fractures (P = 0.01), and retained the similar adverse events (P = 0.86). Bisphosphonates may provide protection and safety against bone mineral loss in IBD patients.
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Affiliation(s)
- Liwei Yao
- Department of Orthopaedic Surgery, The Affiliated Hospital of School of Medicine of Ningbo University
| | - Haiqing Wang
- Department of Foot and Ankle Surgery, Ningbo No. 6 Hospital, Ningbo, Zhejiang, China
| | - Wenwei Dong
- Department of Orthopaedic Surgery, The Affiliated Hospital of School of Medicine of Ningbo University
| | - Zhenxin Liu
- Department of Orthopaedic Surgery, The Affiliated Hospital of School of Medicine of Ningbo University
| | - Haijiao Mao
- Department of Orthopaedic Surgery, The Affiliated Hospital of School of Medicine of Ningbo University
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Genetics, Mucosal Inflammation and the Environment in Post-Infectious Chronic Gut Syndromes. ACTA ACUST UNITED AC 2016. [DOI: 10.1038/ajgsup.2016.14] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Yun-Kai L, Hui W, Xin-wei Z, Liang G, Jin-liang Z. The polymorphism of Insulin-like growth factor-I (IGF-I) is related to osteoporosis and bone mineral density in postmenopausal population. Pak J Med Sci 2014; 30:131-5. [PMID: 24639846 PMCID: PMC3955557 DOI: 10.12669/pjms.301.4264] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2013] [Revised: 10/19/2013] [Accepted: 10/22/2013] [Indexed: 11/27/2022] Open
Abstract
OBJECTIVE It has been shown that Insulin-like growth factor-1 (IGF-1) may be related with bone mineral density (BMD) or osteoporosis. But there are few evidences on the role of genetic variation of IGF-1 on the BMD or osteoporosis. We observed the relationship between polymorphisms of IGF-1(rs35767, rs2288377 and rs5742612) with osteoporosis and BMD in the postmenopausal female population in our study. METHODS A total of 216 postmenopausal women with a primary diagnosis of osteoporosis and 220 normal healthy women were included in the study. Genomic DNA of IGF-1 rs35767, rs2288377 and rs5742612 was extracted from the whole blood using QIAamp blood DNA mini kits (QIAGEN, Hilden, Germany) according to the methods recommended by the manufacturer. RESULTS We found that T allele of rs35767 had higher increased risk of osteoporosis (OR=1.34, 95%CI=1.0-1.81). Those carrying T allele of rs35767 had a significant lower BMD at L1-L4 vertebrae, femoral neck, total hip and trochanter when compared with those carrying C allele (P < 0.05). In addition, the BMD of L1-L4 vertebrae, femoral neck, total hip and trochanter decreased by 2.09%, 3.74%, 3.52% and 2.54% in women carrying T alleles compared with those carrying C alleles. CONCLUSION Our study suggests that polymorphism in IGF-I rs35767 was significantly associated with BMD and osteoporosis in postmenopausal female population, and polymorphism of rs35767 could be a marker for lower BMD and risk of osteoporosis.
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Affiliation(s)
- Li Yun-Kai
- Li Yun-Kai, The Fifth Surgical Department, The Fourth People’s Hospital, Jinan, 250013, China
| | - Wang Hui
- Wang Hui, Department of Stomatology, Jinan Traditional Chinese Medicine Hospital,Jinan, 250012, China
| | - Zhu Xin-wei
- Zhu Xin-wei, The Fifth Surgical Department, The Fourth People’s Hospital, Jinan, 250013, China
| | - Guo Liang
- Guo Liang, Department of Radiotherapy, The Fourth People’s Hospital, Jinan, 250013, China
| | - Zuo Jin-liang
- Zuo Jin-liang, The Fifth Surgical Department, The Fourth People’s Hospital, Jinan, 250013, China
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Xue LN, Xu KQ, Zhang W, Wang Q, Wu J, Wang XY. Associations between vitamin D receptor polymorphisms and susceptibility to ulcerative colitis and Crohn's disease: a meta-analysis. Inflamm Bowel Dis 2013; 19:54-60. [PMID: 22467262 DOI: 10.1002/ibd.22966] [Citation(s) in RCA: 82] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Several polymorphisms have been identified in the vitamin D receptor (VDR) gene, while their roles in the incidence of ulcerative colitis (UC) and Crohn's disease (CD) are conflicting. This meta-analysis was designed to clarify the impact of these polymorphisms on UC and CD risk. METHODS The PubMed, Embase, and Cochrane electronic databases were searched from February 1995 to August 2011 for studies on the four VDR polymorphisms: TaqI, BsmI, FokI, and ApaI. Data were extracted and pooled odd ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. RESULTS Nine studies were included. In Asians, the ff genotype of FokI was associated with increased UC risk (OR = 1.65; 95% CI, 1.11- 2.45). The "a" allele carrier status of ApaI appeared to be a protective factor for CD (OR = 0.81; 95% CI, 0.67-0.97). The tt genotype increased the risk of CD in Europeans (OR = 1.23; 95% CI, 1.02-1.49). Moreover, the tt genotype of TaqI in males had a moderate elevated risk of UC (OR = 1.56; 95% CI, 1.02-2.39) and CD (OR = 1.84; 95% CI, 1.19-2.83). CONCLUSIONS The meta-analysis reveals a significant increase in CD risk for Europeans carrying TaqI tt genotype and a significant decrease in CD risk for all carriers of the Apal "a" allele. For Asians, the VDR FokI polymorphism appears to confer susceptibility to UC. For males, the TaqI tt genotype is associated with susceptibilities to both UC and CD. Our study explored the genetic risk prediction in UC and CD, and may provide valuable insights into IBD therapy.
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Affiliation(s)
- Le-Ning Xue
- Department of Gastroenterology, Changzhou No 2 Hospital, Affiliated with Nanjing Medical University, Changzhou City, Jiangsu Province, China
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Tural S, Kara N, Alayli G, Tomak L. Association between osteoporosis and polymorphisms of the bone Gla protein, estrogen receptor 1, collagen 1-A1 and calcitonin receptor genes in Turkish postmenopausal women. Gene 2012; 515:167-72. [PMID: 23137636 DOI: 10.1016/j.gene.2012.10.041] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2012] [Revised: 09/06/2012] [Accepted: 10/10/2012] [Indexed: 01/26/2023]
Abstract
In this study, we have investigated the association between osteoporosis and osteocalcin (BGLAP) -298 C>T, estrogen receptor 1 (ER1) 397 T>C, collagen type1 alpha 1 (Col1A1) 2046 G>T and calcitonin receptor (CALCR) 1340 T>C polymorphisms. Genomic DNA was obtained from 266 persons (158 osteoporotic and 108 healthy controls). Genomic DNA was extracted from EDTA-preserved peripheral venous blood of patients and controls by a salting-out method and analyzed by PCR-RFLP. As a result, there was no statistically significant difference in the genotype and allele frequencies of patients and controls for BGLAP -298 C>T, Col1A1 2046 G>T, ER1 397 T>C and CALCR 1340 T>C polymorphisms. However, ER1 CC genotype compared with TT+TC genotypes was found to increase the two fold the risk of osteoporosis [p=0.039, OR=2.156, 95% CI (1.083-4.293)] and CALCR CC genotype compared with TT+TC genotypes was found to have protective effect against osteoporosis [p=0.045, OR=0.471, 95% CI (0.237-0.9372)]. In the combined genotype analysis, ER1/CALCR TCCC combined genotype was estimated to have protective effect against osteoporosis [p=0.0125, OR=0.323, 95% CI (0.1383-0.755)] whereas BGLAP/Col1A1 CCTT and ER1/CALCR CCTT combined genotypes were estimated as risk factors for osteoporosis in Turkish population (p=0.027, p=0.009 respectively).
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Affiliation(s)
- Sengul Tural
- Ondokuz Mayis University, Faculty of Medicine, Dept. of Medical Biology and Genetics, Samsun, Turkey.
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Is there any relation between IL-6 gene −174 G>C polymorphism and postmenopausal osteoporosis? Eur J Obstet Gynecol Reprod Biol 2012; 164:98-101. [DOI: 10.1016/j.ejogrb.2012.05.026] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2011] [Revised: 04/19/2012] [Accepted: 05/13/2012] [Indexed: 01/08/2023]
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Soo I, Siffledeen J, Siminoski K, McQueen B, Fedorak RN. Risedronate improves bone mineral density in Crohn's disease: a two year randomized controlled clinical trial. J Crohns Colitis 2012; 6:777-86. [PMID: 22398088 DOI: 10.1016/j.crohns.2012.01.004] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2011] [Revised: 01/04/2012] [Accepted: 01/04/2012] [Indexed: 02/08/2023]
Abstract
BACKGROUND Patients with Crohn's disease have an increased frequency of osteopenia and osteoporosis. This randomized, controlled, double-blind study assessed the efficacy of risedronate versus placebo in treating low bone mineral density (BMD) in patients with Crohn's disease. METHODS 88 Crohn's disease outpatients with BMD T-score<-1.0 by dual-energy X-ray absorptiometry were randomly assigned to one of two treatment groups for the two year study duration: one group received risedronate 35 mg weekly while another received placebo. Both groups received daily calcium (Ca; 500 mg) and vitamin D (D; 400 IU) supplementation. Percent change in BMD relative to baseline was compared between the two therapies at 12 and 24 months. RESULTS Using intent-to-treat analysis, at 12 months, risedronate+Ca+D increased BMD, relative to baseline, more than placebo+Ca+D in the femoral trochanter (1.4±3.4% vs -0.1±3.1%; p=0.03) and total hip (1.1±2.7% vs -0.1±2.5%;p=0.04). This trend in greater BMD continued for the 24 month duration of the study. There was no difference between the two treatment groups for changes in spine BMD. Subgroup analysis revealed that risedronate+Ca+D resulted in significantly better improvement in femoral trochanter BMD in non-smokers (p=0.01), males (p=0.01), those with a history of corticosteroid use in the preceding year (p=0.01), and current users of immunosuppressants (p=0.04). CONCLUSIONS Risedronate, in addition to daily calcium and vitamin D supplementation, is superior to calcium and vitamin D alone in improving femoral trochanter and total hip BMD in patients with Crohn's disease.
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Affiliation(s)
- Isaac Soo
- Division of Gastroenterology, University of Alberta, Edmonton, Alberta, Canada
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Tsianos EV, Katsanos KH, Tsianos VE. Role of genetics in the diagnosis and prognosis of Crohn's disease. World J Gastroenterol 2012; 18:105-18. [PMID: 22253516 PMCID: PMC3257437 DOI: 10.3748/wjg.v18.i2.105] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2011] [Revised: 04/25/2011] [Accepted: 05/02/2011] [Indexed: 02/06/2023] Open
Abstract
Considering epidemiological, genetic and immunological data, we can conclude that the inflammatory bowel diseases are heterogeneous disorders of multifactorial etiology in which hereditability and environment interact to produce the disease. It is probable that patients have a genetic predisposition for the development of the disease coupled with disturbances in immunoregulation. Several genes have been so far related to the diagnosis of Crohn's disease. Those genes are related to innate pattern recognition receptors, to epithelial barrier homeostasis and maintenance of epithelial barrier integrity, to autophagy and to lymphocyte differentiation. So far, the most strong and replicated associations with Crohn's disease have been done with NOD2, IL23R and ATG16L1 genes. Many genes have so far been implicated in prognosis of Crohn's disease and many attempts have been made to classify genetic profiles in Crohn's disease. CARD15 seems not only a susceptibility gene, but also a disease-modifier gene for Crohn's disease. Enriching our understanding on Crohn's disease genetics is important but when combining genetic data with functional data the outcome could be of major importance to clinicians.
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Tsianos EV, Katsanos KH, Tsianos VE. Role of genetics in the diagnosis and prognosis of Crohn's disease. World J Gastroenterol 2011; 17:5246-59. [PMID: 22219593 PMCID: PMC3247688 DOI: 10.3748/wjg.v17.i48.5246] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2011] [Revised: 06/15/2011] [Accepted: 06/22/2011] [Indexed: 02/06/2023] Open
Abstract
Considering the epidemiological, genetic and immunological data, we can conclude that the inflammatory bowel diseases are heterogeneous disorders of multifactorial etiology in which hereditability and environment interact to produce the disease. It is probable that patients have a genetic predisposition for the development of the disease coupled with disturbances in immunoregulation. Several genes have so far been related to the diagnosis of Crohn's disease. These genes are related to innate pattern recognition receptors, to epithelial barrier homeostasis and maintenance of epithelial barrier integrity, to autophagy and to lymphocyte differentiation. So far, the strongest and most replicated associations with Crohn's disease have been demonstrated with NOD2, IL23R and ATG16L1 genes. Many genes have so far been implicated in the prognosis of Crohn's disease and many attempts have been made for classification of genetic profiles in Crohn's disease. CARD15 seems to be not only a susceptibility gene, but also a disease-modifier gene for Crohn's disease. Enriching our understanding of Crohn's disease genetics is of value, but when combining genetic data with functional data the outcome could be of major importance to clinicians.
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Klaus J, Haenle MM, Schröter C, Adler G, von Boyen G, Reinshagen M, von Tirpitz C. A single dose of intravenous zoledronate prevents glucocorticoid therapy-associated bone loss in acute flare of Crohn's disease, a randomized controlled trial. Am J Gastroenterol 2011; 106:786-93. [PMID: 21386830 DOI: 10.1038/ajg.2011.59] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES To assess the effectiveness and safety of zoledronate (ZOL) in preventing glucocorticoid therapy-associated bone loss in patients with acute flare of Crohn's disease (CD) in a randomized, double-blind, placebo-controlled trial. METHODS Forty CD patients starting a glucocorticoid therapy (60 mg prednisolone per day) for acute flare (CD activity index (CDAI) >220) were randomized to compare the effect of ZOL (4 mg intravenous, n=20) or placebo (n=20) on change in lumbar bone mineral density (BMD). All patients received calcium citrate (800 mg) and colecalciferol (1,000 IU) daily. Dual energy X-ray absorptiometry (DXA) of the lumbar spine (L1-L4) was performed at baseline and day 90. Follow-up examinations at day 1/7/14/30 and 90 included laboratory tests and adverse event/serious adverse events reports. RESULTS Thirty-six patients were available for per-protocol analysis. With placebo (n=18), a decrease in BMD was seen (T-score: -0.98 ± 0.8, day 0 and -1.25 ± 0.77, day 90, P=0.06), with ZOL (n=18) BMD increased (-1.15 ± 1.02, day 0 and -0.74 ± 1.09, day 90, P=0.03). The change in BMD under placebo (-0.26 ± 0.21) vs. ZOL (+0.41 ± 0.19) was highly significant (P=0.006). In all, 14 out of 18 patients with ZOL had an increase in BMD (+0.64 ± 0.48), 12 of 18 with placebo a decrease (-0.50 ± 0.39). Changes of clinical findings and laboratory results of inflammation (leukocytes, platelets, and C-reactive protein) were the same in- and between-groups throughout the study. With ZOL, serum bone degradation marker β-Cross-Laps decreased. Study medication was safe and well tolerated. CONCLUSIONS ZOL is effective in preventing glucocorticoid therapy-induced bone loss in patients with acute flare of CD and should be considered whenever a glucocorticoid therapy is started in CD patients.
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Affiliation(s)
- Jochen Klaus
- Department of Internal Medicine I, University of Ulm, Ulm, Germany.
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Klaus J, Reinshagen M, Herdt K, Schröter C, Adler G, Boyen GBTV, Tirpitz CV. Bones and Crohn's: no benefit of adding sodium fluoride or ibandronate to calcium and vitamin D. World J Gastroenterol 2011; 17:334-42. [PMID: 21253392 PMCID: PMC3022293 DOI: 10.3748/wjg.v17.i3.334] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2010] [Revised: 10/15/2010] [Accepted: 10/22/2010] [Indexed: 02/06/2023] Open
Abstract
AIM To compare the effect of calcium and cholecalciferol alone and along with additional sodium fluoride or ibandronate on bone mineral density (BMD) and fractures in patients with Crohn's disease (CD). METHODS Patients (n =148) with reduced BMD (T-score < -1) were randomized to receive cholecalciferol (1000 IU) and calcium citrate (800 mg) daily alone(group A, n = 32) or along with additional sodium fluoride (25 mg bid) (group B, n = 62) or additional ibandronate (1 mg iv/3-monthly) (group C, n = 54). Dual energy X-ray absorptiometry of the lumbar spine (L1-L4) and proximal right femur and X-rays of the spine were performed at baseline and after 1.0, 2.25 and 3.5 years. Fracture-assessment included visual reading of X-rays and quantitative morphometry of vertebral bodies (T4-L4). RESULTS One hundred and twenty three (83.1%) patients completed the first year for intention-to-treat (ITT) analysis. Ninety two (62.2%) patients completed the second year and 71 (47.8%) the third year available for per-protocol (PP) analysis. With a significant increase in T-score of the lumbar spine by +0.28 ± 0.35 [95% confidence interval (CI): 0.162-0.460, P < 0.01], +0.33 ± 0.49 (95% CI: 0.109-0.558, P < 0.01), +0.43 ± 0.47 (95% CI: 0.147-0.708, P < 0.01) in group A, +0.22 ± 0.33 (95% CI: 0.125-0.321, P < 0.01); +0.47 ± 0.60 (95% CI: 0.262-0.676, P < 0.01), +0.51 ± 0.44 (95% CI: 0.338-0.682, P < 0.01) in group B and +0.22 ± 0.38 (95% CI: 0.111-0.329, P < 0.01), +0.36 ± 0.53 (95% CI: 0.147-0.578, P < 0.01), +0.41 ± 0.48 (95% CI: 0.238-0.576, P < 0.01) in group C, respectively, during the 1.0, 2.25 and 3.5 year periods (PP analysis), no treatment regimen was superior in any in- or between-group analyses. In the ITT analysis, similar results in all in- and between-group analyses with a significant in-group but non-significant between-group increase in T-score of the lumbar spine by 0.38 ± 0.46 (group A, P < 0.01), 0.37 ± 0.50 (group B, P < 0.01) and 0.35 ± 0.49 (group C, P < 0.01) was observed. Follow-up in ITT analysis was still 2.65 years. One vertebral fracture in the sodium fluoride group was detected. Study medication was safe and well tolerated. CONCLUSION Additional sodium fluoride or ibandronate had no benefit over calcium and cholecalciferol alone in managing reduced BMD in CD.
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Schmidt S, Mellström D, Norjavaara E, Sundh V, Saalman R. Familial resemblance of bone mineral density in children with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2010; 51:146-50. [PMID: 20531019 DOI: 10.1097/mpg.0b013e3181dbf42c] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND AND AIM Low bone mineral density (BMD) has recently been recognized as a potential health problem in children with inflammatory bowel disease (IBD). Our aim was to investigate the familial resemblance of BMD in pediatric patients with IBD. PATIENTS AND METHODS In this population-based study from western Sweden, we assessed 144 children with IBD, 83 with ulcerative colitis, 45 with Crohn disease, 16 with indeterminate colitis, and their parents (136 mothers and 130 fathers) with dual-energy X-ray absorptiometry (DEXA). After adjustment for sex, age, weight, height, and parental IBD, we correlated the BMD of the patients to the BMD of their mothers, fathers, and the midparent value ([mother's BMD + father's BMD]/2) at different skeletal sites and calculated the Pearson correlation coefficient (r) to evaluate the extent of familial resemblance. RESULTS The BMD of the children with IBD was clearly related to the BMD of their parents. The strongest correlation was found in the femoral neck with r = 0.55 (P < 0.001, 95% CI 0.41-0.66) between BMD of the children and the midparent value. The group of children with IBD had an odds ratio of 5.96 for decreased BMD (lumbar spine z score < -1 standard deviation) given that decreased BMD was diagnosed in both parents. CONCLUSIONS We conclude that BMD in children and adolescents with IBD is significantly related to that of their parents. In a clinical setting, it may be helpful to assess the parents of children with IBD with DEXA to interpret the children's DEXA measurements.
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Affiliation(s)
- Susanne Schmidt
- Department of Pediatrics, Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
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17
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Silva APD, Karunanayake AL, Dissanayaka TGI, Dassanayake AS, Duminda HKKT, Pathmeswaran A, Wickramasinghe AR, Silva HJD. Osteoporosis in adult Sri Lankan inflammatory bowel disease patients. World J Gastroenterol 2009; 15:3528-31. [PMID: 19630109 PMCID: PMC2715980 DOI: 10.3748/wjg.15.3528] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.7] [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
AIM: To determine if inflammatory bowel disease (IBD) is a risk factor for osteoporosis in adult Sri Lankans.
METHODS: We identified eligible subjects from among consecutive patients diagnosed with IBD who attended our outpatient clinic. We included only patients aged between 20 and 70 years. Patients who were pregnant, had significant comorbidity, or were on calcium supplements or treatment for osteoporosis within the past 6 mo, were excluded. Healthy, age- and sex-matched controls were also recruited, in a control to patient ratio of 3:1. Both groups were screened for osteoporosis using peripheral dual energy X-ray absorptiometry scanning.
RESULTS: The study population consisted of 111 IBD patients (male:female = 43:68; mean age 42.5 years) and 333 controls (male:female = 129:204; mean age 43.8 years). The occurrence of osteoporosis among IBD patients (13.5%) was significantly higher than among controls (4.5%) (P = 0.001). The frequency of osteoporosis was not significantly different between ulcerative colitis (14.45%) and Crohn’s disease (10.7%). However, on multivariate analysis, only age (P = 0.001), menopause (P = 0.024) and use of systemic steroids (P < 0.001) were found to be associated independently with the occurrence of osteoporosis, while IBD, severity of disease, number of relapses, duration of illness or treatment other than systemic steroids were not.
CONCLUSION: IBD does not appear to be an independent risk factor for the occurrence of osteoporosis in this population. However, the use of systemic steroids was a risk factor.
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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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Abstract
Half of all patients with inflammatory bowel disease show a significant reduction of their bone mass during the course of their chronic inflammatory disease. In contrast to women with postmenopausal osteoporosis these patients are much younger and a significant subgroup develops vertebral fractures which are mostly asymptomatic. The activity of the chronic inflammatory disease and the steroid treatment leads to bone loss predominantly through the TNFα-driven osteoprotegerin system. Clinical useful genetic markers to identify patients at risk for fractures have not been developed so far. Long-term clinical remission leads in most patients to normalisation of the bone density. Patients with reduced bone density should be substituted with calcium and vitamin D. Patients with vertebral fractures should receive bisphosphonates.
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Affiliation(s)
- Max Reinshagen
- Department of Medicine I, Klinikum Braunschweig, Germany
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Zhu X, Luo J, Chen X, Wang J, Wang G, Li H, Xu Y, Feng J, Tu H. Expression characteristic and significance of interleukin-6, nuclear factor kappa beta, and bone formation markers in rat models of osteoporosis. Transl Res 2008; 152:18-23. [PMID: 18593633 DOI: 10.1016/j.trsl.2008.05.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2008] [Revised: 05/20/2008] [Accepted: 05/22/2008] [Indexed: 01/06/2023]
Abstract
The goal of this study was to investigate the expression levels of interleukin 6 (IL-6), nuclear factor kappa beta (NF-kappabeta), bone-specific alkaline phosphatase (BALP), and bone osteocalcin (BGP) in rats with osteoporosis and their significance in the pathogenesis of osteoporosis. In all, 60 adult female SD rats were divided randomly into 3 groups of 20 rats each: normal control group (control), sham-operated group (sham), and ovariectomized group (OVX). In 2, 3, 4, 5, and 6 months after surgery, 4 rats were randomized from each group for assays of BMD, IL-6, BALP, and BGP. Then, the rats were sacrificed for the detection of IL-6 and NF-kappabeta expression levels in bone tissue by quantitative real-time RT-PCR analysis. Compared with the sham (0.097 +/- 0.04 g/cm2, 0.097 +/- 0.01 g/cm2, 0.095 +/- 0.07 g/cm2) and control group (0.107 +/- 0.01 g/cm2, 0.103 +/- 0.07 g/cm2, 0.108 +/- 0.06 g/cm2), the BMD of rats in the OVX group was reduced remarkably in 4, 5, and 6 months (0.082 +/- 0.05 g/cm2, 0.073 +/- 0.02 g/cm2, 0.061 +/- 0.05 g/cm2, respectively; P < 0.01); the serum IL-6 level increased significantly from 2 to 6 months after surgery (P < 0.01); and the serum levels of BALP and BGP were greater at 4, 5, and 6 months (P < 0.05). The quantitative real-time RT-PCR analysis demonstrated that IL-6 and NF-kappabeta mRNA levels in OVX group increased in a time-dependent manner. Moreover, the IL-6, NF-kappabeta, BALP, and BGP levels were correlated negatively with the BMD. Meanwhile, a positive correlation was observed between IL-6 and NF-kappabeta. In conclusion, the expression levels of IL-6, NF-kappabeta, and bone formation markers may increase significantly in the osteoporosis rats. These molecules could play a role in the pathogenesis.
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Affiliation(s)
- Xiaohu Zhu
- Taihe Hospital of Yunyang Medicine College, Taihe Hospital Rehabilitation Medicine Center, Shiyan, Hubei, China
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Noble CL, McCullough J, Ho W, Lees CW, Nimmo E, Drummond H, Bear S, Hannan J, Millar C, Ralston SH, Satsangi J. Low body mass not vitamin D receptor polymorphisms predict osteoporosis in patients with inflammatory bowel disease. Aliment Pharmacol Ther 2008; 27:588-96. [PMID: 18194505 DOI: 10.1111/j.1365-2036.2008.03599.x] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
BACKGROUND Osteoporosis is a recognized complication of inflammatory bowel disease (IBD). Aim To investigate the role of environmental factors and vitamin D receptor (VDR) variants on the prevalence of osteoporosis. METHODS DEXA scans and case note review were performed on 440 IBD patients from 1997 to 2006. All the IBD patients and 240 healthy controls were genotyped for VDR variants Taq-1 and Apa-1 using PCR-RFLP. RESULTS Osteoporosis and osteopenia rates were 15% and 18% for IBD, 16% and 18% for Crohn's disease (CD) and 13% and 19% for ulcerative colitis, respectively. On univariate analysis of the CD patients, low body mass index (BMI, <18.5) and smoking status (P = 0.008 and 0.005 respectively) were associated with osteoporosis and osteopenia. Low BMI was also associated with osteoporosis on multivariate analysis in CD (P = 0.021, OR 5.83, CI 1.31-25.94). No difference was observed between Taq-1 and Apa-1 VDR polymorphisms in IBD, CD, ulcerative colitis and healthy controls. However, CD males were more likely to carry the variant Taq-1 polymorphism than healthy controls males (P = 0.0018, OR 1.94, CI 1.28-2.92) and female CD patients (P = 0.0061, OR 1.60, CI 1.17-2.44). CONCLUSIONS In this well-phenotyped cohort of IBD patients, a relatively low prevalence of osteoporosis was observed. Low BMI was the only independent risk factor identified to be associated with osteoporosis.
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Affiliation(s)
- C L Noble
- Gastrointestinal Unit, Molecular Medicine Centre, University of Edinburgh, Western General Hospital, Edinburgh, UK.
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Guo Y, Yang TL, Pan F, Xu XH, Dong SS, Deng HW. Molecular genetic studies of gene identification for osteoporosis. Expert Rev Endocrinol Metab 2008; 3:223-267. [PMID: 30764094 DOI: 10.1586/17446651.3.2.223] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
This review comprehensively summarizes the most important and representative molecular genetics studies of gene identification for osteoporosis published up to the end of September 2007. It is intended to constitute a sequential update of our previously published reviews covering the available data up to the end of 2004. Evidence from candidate gene-association studies, genome-wide linkage and association studies, as well as functional genomic studies (including gene-expression microarray and proteomics) on osteogenesis and osteoporosis, are reviewed separately. Studies of transgenic and knockout mice models relevant to osteoporosis are summarized. The major results of all studies are tabulated for comparison and ease of reference. Comments are made on the most notable findings and representative studies for their potential influence and implications on our present understanding of genetics of osteoporosis. The format adopted by this review should be ideal for accommodating future new advances and studies.
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Affiliation(s)
- Yan Guo
- a The Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, PR China
| | - Tie-Lin Yang
- a The Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, PR China
| | - Feng Pan
- a The Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, PR China
| | - Xiang-Hong Xu
- a The Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, PR China
| | - Shan-Shan Dong
- a The Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, PR China
| | - Hong-Wen Deng
- b The Key Laboratory of Biomedical Information Engineering of Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an 710049, PR China and Departments of Orthopedic Surgery and Basic Medical Sciences, University of Missouri - Kansas City, Kansas City, MO 64108, USA.
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Abstract
Inflammatory bowel disease (IBD), comprising Crohn's disease and ulcerative colitis, is associated with an increased risk of osteoporosis and bone fractures. Initial studies suggested very high rates of osteoporosis in IBD, but more recent studies have suggested that bone mineral density (BMD) is often normal in patients with IBD and typically changes little over time. Nonetheless, IBD is associated with an increased risk of fractures. Doctors managing patients with IBD must consider a variety of risk factors, not just BMD measurements, in assessing fracture risk. Advances have been made in exploring the pathogenesis of osteoporosis in IBD. The evolution of knowledge regarding receptor for activated factor of nuclear factor kappaB (RANK), its ligand RANKL, and osteoprotegerin (OPG), which serves as a decoy receptor, has enhanced the understanding of both osteoporosis and T-cell immunobiology. Recent clinical studies in patients with IBD have revealed that serum OPG levels may be elevated and inflamed intestinal tissue secretes increased amounts of OPG. It is suspected that OPG levels are elevated as a counterregulatory response to low BMD, as serum OPG levels in IBD have been found to be inversely associated with BMD. Finally, in animal models of IBD, exogenous OPG has reversed both the osteopenia and the enterocolitis, suggesting that it may have a therapeutic role in human IBD.
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Affiliation(s)
- Charles N Bernstein
- University of Manitoba Inflammatory Bowel Disease Clinical and Research Centre, 804F-715 McDermot Avenue, Winnipeg, Manitoba R3E 3P4, Canada.
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Rankinen T, Zuberi A, Chagnon YC, Weisnagel SJ, Argyropoulos G, Walts B, Pérusse L, Bouchard C. The human obesity gene map: the 2005 update. Obesity (Silver Spring) 2006; 14:529-644. [PMID: 16741264 DOI: 10.1038/oby.2006.71] [Citation(s) in RCA: 706] [Impact Index Per Article: 37.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
This paper presents the 12th update of the human obesity gene map, which incorporates published results up to the end of October 2005. Evidence from single-gene mutation obesity cases, Mendelian disorders exhibiting obesity as a clinical feature, transgenic and knockout murine models relevant to obesity, quantitative trait loci (QTL) from animal cross-breeding experiments, association studies with candidate genes, and linkages from genome scans is reviewed. As of October 2005, 176 human obesity cases due to single-gene mutations in 11 different genes have been reported, 50 loci related to Mendelian syndromes relevant to human obesity have been mapped to a genomic region, and causal genes or strong candidates have been identified for most of these syndromes. There are 244 genes that, when mutated or expressed as transgenes in the mouse, result in phenotypes that affect body weight and adiposity. The number of QTLs reported from animal models currently reaches 408. The number of human obesity QTLs derived from genome scans continues to grow, and we now have 253 QTLs for obesity-related phenotypes from 61 genome-wide scans. A total of 52 genomic regions harbor QTLs supported by two or more studies. The number of studies reporting associations between DNA sequence variation in specific genes and obesity phenotypes has also increased considerably, with 426 findings of positive associations with 127 candidate genes. A promising observation is that 22 genes are each supported by at least five positive studies. The obesity gene map shows putative loci on all chromosomes except Y. The electronic version of the map with links to useful publications and relevant sites can be found at http://obesitygene.pbrc.edu.
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Affiliation(s)
- Tuomo Rankinen
- Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA 70808-4124, USA
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