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KMID : 0667720070440000494
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Report Natlonal Institute of Health
2007 Volume.44 No. 0 p.494 ~ p.497
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Association study to discover T2DM-related genetic polymorphism
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Go Min-Jin
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Abstract
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Purpose : We aimed to verify the association between type 2 diabetes mellitus (T2DM) and 20 single nucleotide polymorphisms (SNPs) which have been identified as genetic risk factors for T2DM in the European populations.
Methods : A total of 20 SNPs from 12 T2DM candidate genes were genotyped from 5,244 normal, 1,385 impaired glucose tolerance (IGT), and 771 T2DM subjects in Ansung and Ansan community cohorts by TaqMan method. Resulting genotyping data were used for T2DM case-control association analysis in order to identify genetic
associations of cadiate SNPs with T2DM.
Results : Average genotype call rate and reproducibility of the TaqMan experiment were 99.4% and 100%, respectively. In a total 7,468 samples, 9 of 20 SNPs showed their minor allele frequencies (MAF) less than 0.05 and all 20 SNPs satisfied Hardy Weinberg Equilibrium (HWE) test. Similar results in MAF and HWE test were observed in each sample group such as normal, IGT, and T2DM. To clarify genetic basis related to IGT and T2DM, our case-control studies were further stratified into normal/IGT, IGT/T2DM, normal/T2DM, normal/IGT+T2DM, and normal+IGT/T2DM
groups. Primary logistic regression was analyzed to identify significant SNPs in each case-control study by adjusting age and sex. Additional analyses were performed by adjusting age, sex and BMI, or by adjusting age, sex, BMI and fasting glucose. Normal/IGT case-control study detected GCK-rs1799884, HNF4A-rs1884614, INSIG2-rs7566605, KCNJ11-rs5129, and TCF7L2-rs12255372 as significant genetic factors that are related to normal IGT transition. IGT/T2DM study identified
PPARG-rs1801282. Normal/T2DM study identified PPARG-rs1801282, GCK-rs1799884, HNF4A-rs1884614, INSIG2-rs7566605, and KCNJ11-rs5129. Normal/IGT+T2DM study detected GCK-rs1799884, HNF4A-rs1884614, INSIG2-rs7566605, KCNJ11-rs5129, and TCF7L2-rs12255372. In normal+IGT/T2DM, PPARG-rs1801282, GCK-rs1799884, and HNF4A-rs1884614 were detected as T2DM realted SNPs.
Conclusions : We identified not only SNPs that are associated with T2DM, but also those related to IGT-T2DM transition. These results will be useful in the future in developing a prediction model for T2DM.
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KEYWORD
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Single nucleotide polymorphisms (SNPs), Impaired glucose tolerance (IGT), Type 2 diabetes mellitus (T2DM), Case-control study
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