Document Detail


Implication of genetic variants near NEGR1, SEC16B, TMEM18, ETV5/DGKG, GNPDA2, LIN7C/BDNF, MTCH2, BCDIN3D/FAIM2, SH2B1, FTO, MC4R, and KCTD15 with obesity and type 2 diabetes in 7705 Chinese.
MedLine Citation:
PMID:  20215397     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Recent genome-wide association studies have identified multiple novel loci associated with obesity in Europeans. We hypothesized that these genetic variants may be associated with obesity and type 2 diabetes (T2D) in Chinese. RESEARCH DESIGN AND METHODS: We examined 14 associated single-nucleotide polymorphisms at 12 loci (NEGR1, SEC16B, TMEM18, ETV5/DGKG, GNPDA2, LIN7C/BDNF, MTCH2, BCDIN3D/FAIM2, SH2B1, FTO, MC4R, and KCTD15) in 605 healthy adults, 1087 healthy adolescents and 6013 T2D patients from Hong Kong. RESULTS: The European at-risk alleles at five loci including GNPDA2, BCDIN3D/FAIM2, SH2B1, FTO, and KCTD15 were significantly associated with increased body mass index (BMI), waist circumference (4.5 x 10(-8) < P < 0.024), and/or obesity risk (odds ratio 1.14-1.22, 2.0 x 10(-5) < P < 0.002) in our Chinese populations. The former four loci as well as LIN7C/BDNF were also modestly associated with T2D risk (odds ratio 1.09-1.22, 0.008 < P < 0.041), but the associations were lost after adjustment for BMI, suggesting their roles in T2D risk are mediated through modulation of adiposity. Joint effect analyses of the five adiposity loci revealed an increase of about 0.29 kg/m(2) in BMI with each additional copy of at-risk allele (P(trend) = 4.2 x 10(-12)). CONCLUSIONS: Our findings support the important contribution of GNPDA2, BCDIN3D/FAIM2, SH2B1, FTO, and KCTD15 in the regulation of adiposity, which in turn affects T2D risk in Chinese.
Authors:
Maggie C Y Ng; Claudia H T Tam; Wing Yee So; Janice S K Ho; Alfred W Chan; Heung Man Lee; Ying Wang; Vincent K L Lam; Juliana C N Chan; Ronald C W Ma
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-09
Journal Detail:
Title:  The Journal of clinical endocrinology and metabolism     Volume:  95     ISSN:  1945-7197     ISO Abbreviation:  J. Clin. Endocrinol. Metab.     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-06     Completed Date:  2010-05-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0375362     Medline TA:  J Clin Endocrinol Metab     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2418-25     Citation Subset:  AIM; IM    
Affiliation:
Department of Medicine and Therapeutics, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China.
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MeSH Terms
Descriptor/Qualifier:
Adaptor Proteins, Signal Transducing / genetics
Apoptosis Regulatory Proteins / genetics
Asian Continental Ancestry Group / genetics
Brain-Derived Neurotrophic Factor / genetics
Cell Adhesion Molecules, Neuronal / genetics
China
DNA-Binding Proteins / genetics
Diabetes Mellitus, Type 2 / genetics*
Genetic Variation*
Humans
Membrane Proteins / genetics
Obesity / genetics*
Potassium Channels, Voltage-Gated / genetics
Protein Disulfide-Isomerases / genetics
Proteins / genetics
Receptor, Melanocortin, Type 4 / genetics
Transcription Factors / genetics
Vesicular Transport Proteins / genetics
Chemical
Reg. No./Substance:
0/Adaptor Proteins, Signal Transducing; 0/Apoptosis Regulatory Proteins; 0/Brain-Derived Neurotrophic Factor; 0/Cell Adhesion Molecules, Neuronal; 0/DNA-Binding Proteins; 0/ETV5 protein, human; 0/FAIM2 protein, human; 0/FTO protein, human; 0/MC4R protein, human; 0/Membrane Proteins; 0/NEGR1 protein, human; 0/Potassium Channels, Voltage-Gated; 0/Proteins; 0/Receptor, Melanocortin, Type 4; 0/SH2B1 protein, human; 0/TMEM18 protein, human; 0/Transcription Factors; 0/Vesicular Transport Proteins; EC 5.3.4.1/PDIA2 protein, human; EC 5.3.4.1/Protein Disulfide-Isomerases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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