Background: Type 2 diabetes mellitus (T2DM) is a complex endocrine and metabolic disorder. Recently, several\r\ngenome-wide association studies (GWAS) have identified many novel susceptibility loci for T2DM, and indicated\r\nthat there are common genetic causes contributing to the susceptibility to T2DM in multiple populations\r\nworldwide. In addition, clinical and epidemiological studies have indicated that obesity is a major risk factor for\r\nT2DM. However, the prevalence of obesity varies among the various ethnic groups. We aimed to determine the\r\ncombined effects of these susceptibility loci and obesity/overweight for development of T2DM in the Japanese.\r\nMethods: Single nucleotide polymorphisms (SNPs) in or near 17 susceptibility loci for T2DM, identified through\r\nGWAS in Caucasian and Asian populations, were genotyped in 333 cases with T2DM and 417 control subjects.\r\nResults: We confirmed that the cumulative number of risk alleles based on 17 susceptibility loci for T2DM was an\r\nimportant risk factor in the development of T2DM in Japanese population (P < 0.0001), although the effect of each\r\nrisk allele was relatively small. In addition, the significant association between an increased number of risk alleles\r\nand an increased risk of T2DM was observed in the non-obese group (P < 0.0001 for trend), but not in the obese/\r\noverweight group (P = 0.88 for trend).\r\nConclusions: Our findings indicate that there is an etiological heterogeneity of T2DM between obese/overweight\r\nand non-obese subjects.
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