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KMID : 0620920130450020004
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Experimental & Molecular Medicine
2013 Volume.45 No. 2 p.4 ~ p.0
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Identification of a genetic locus on chromosome 4q34-35 for type 2 diabetes with overweight
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Park Mi-Hyun
Kwak Soo-Heon
Kim Kwang-Joong
Go Min-Jin
Lee Hye-Ja
Kim Kyung-Seon
Hwang Joo-Yeon
Kuchan Kimm
Cho Young-Min
Lee Hong-Kyu
Park Kyong-Soo
Lee Jong-Young
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Abstract
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The incidence of type 2 diabetes is rising rapidly because of an increase in the incidence of being overweight and obesity. Identification of genetic determinants for complex diseases, such as type 2 diabetes, may provide insight into disease pathogenesis. The aim of the study was to investigate the shared genetic factors that predispose individuals to being overweight and developing type 2 diabetes. We conducted genome-wide linkage analyses for type 2 diabetes in 386 affected individuals (269 sibpairs) from 171 Korean families and association analyses with single-nucleotide polymorphisms of candidate genes within linkage regions to identify genetic variants that predispose individuals to being overweight and developing type 2 diabetes. Through fine-mapping analysis of chromosome 4q34-35, we detected a locus potentially linked (nonparametric linkage 2.81, logarithm of odds 2.27, P=6 × 10?4) to type 2 diabetes in overweight or obese individuals (body mass index, BMIgreater than or equal to23?kg?m?2). Multiple regression analysis with type 2 diabetes-related phenotypes revealed a significant association (false discovery rate (FDR) P=0.006 for rs13144140; FDR P=0.002 for rs6830266) between GPM6A (rs13144140) and BMI and waist?hip ratio, and between NEIL3 (rs6830266) and insulin level from 1314 normal individuals. Our systematic search of genome-wide linkage and association studies, demonstrate that a linkage peak for type 2 diabetes on chromosome 4q34-35 contains two type 2 diabetes-related genes, GPM6A and NEIL3.
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KEYWORD
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affected sibpairs, association, linkage, obesity, overweight, type 2 diabetes
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