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Implication of genetic variants near TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/B, IGF2BP2, and FTO in type 2 diabetes and obesity in 6,719 Asians

Cited 274 time in Web of Science Cited 291 time in Scopus
Authors
Ng, Maggie C Y; Park, Kyong Soo; Oh, Bermseok; Tam, Claudia H T; Cho, Young Min; Shin, Hyoung Doo; Lam, Vincent K L; Ma, Ronald C W; So, Wing Yee; Cho, Yoon Shin; Kim, Hyung-Lae; Lee, Hong Kyu; Chan, Juliana C N; Cho, Nam H
Issue Date
2008-05-13
Publisher
American Diabetes Association
Citation
Diabetes. 57(8):2226-2233
Keywords
AdultAgedAllelesAsian Continental Ancestry Group/*geneticsCation Transport Proteins/geneticsCyclin-Dependent Kinase 5/geneticsCyclin-Dependent Kinase Inhibitor p15/geneticsCyclin-Dependent Kinase Inhibitor p16/geneticsDiabetes Mellitus, Type 2/ethnology/*geneticsFemaleGene FrequencyGenetic Predisposition to Disease/ethnology/geneticsGenotypeHomeodomain Proteins/geneticsHong Kong/epidemiologyHumansKorea/epidemiologyMaleMiddle AgedObesity/ethnology/*genetics*Polymorphism, Single NucleotideRNA-Binding Proteins/geneticsTCF Transcription Factors/geneticsTranscription Factors/genetics
Abstract
OBJECTIVE: Recent genome-wide association studies have identified six novel genes for type 2 diabetes and obesity and confirmed TCF7L2 as the major type 2 diabetes gene to date in Europeans. However, the implications of these genes in Asians are unclear. RESEARCH DESIGN AND METHODS: We studied 13 associated single nucleotide polymorphisms from these genes in 3,041 patients with type 2 diabetes and 3,678 control subjects of Asian ancestry from Hong Kong and Korea. RESULTS: We confirmed the associations of TCF7L2, SLC30A8, HHEX, CDKAL1, CDKN2A/CDKN2B, IGF2BP2, and FTO with risk for type 2 diabetes, with odds ratios ranging from 1.13 to 1.35 (1.3 x 10(-12) < P(unadjusted) < 0.016). In addition, the A allele of rs8050136 at FTO was associated with increased BMI in the control subjects (P(unadjusted) = 0.008). However, we did not observe significant association of any genetic variants with surrogate measures of insulin secretion or insulin sensitivity indexes in a subset of 2,662 control subjects. Compared with subjects carrying zero, one, or two risk alleles, each additional risk allele was associated with 17% increased risk, and there was an up to 3.3-fold increased risk for type 2 diabetes in those carrying eight or more risk alleles. Despite most of the effect sizes being similar between Asians and Europeans in the meta-analyses, the ethnic differences in risk allele frequencies in most of these genes lead to variable attributable risks in these two populations. CONCLUSIONS: Our findings support the important but differential contribution of these genetic variants to type 2 diabetes and obesity in Asians compared with Europeans.
ISSN
1939-327X (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18469204

http://diabetes.diabetesjournals.org/content/57/8/2226.full.pdf

https://hdl.handle.net/10371/67868
DOI
https://doi.org/10.2337/db07-1583
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College of Medicine/School of Medicine (의과대학/대학원)Internal Medicine (내과학전공)Journal Papers (저널논문_내과학전공)
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