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The combined effect of the T2DM susceptibility genes is an important risk factor for T2DM in non-obese Japanese: a population based case-control study

DOI: 10.1186/1471-2350-13-11

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Abstract:

Single nucleotide polymorphisms (SNPs) in or near 17 susceptibility loci for T2DM, identified through GWAS in Caucasian and Asian populations, were genotyped in 333 cases with T2DM and 417 control subjects.We confirmed that the cumulative number of risk alleles based on 17 susceptibility loci for T2DM was an important risk factor in the development of T2DM in Japanese population (P < 0.0001), although the effect of each risk allele was relatively small. In addition, the significant association between an increased number of risk alleles and an increased risk of T2DM was observed in the non-obese group (P < 0.0001 for trend), but not in the obese/overweight group (P = 0.88 for trend).Our findings indicate that there is an etiological heterogeneity of T2DM between obese/overweight and non-obese subjects.Type 2 diabetes mellitus (T2DM) is a complex endocrine and metabolic disorder. The interaction between multiple genetic and environmental factors is considered to contribute to the pathogenesis of the disease [1-3]. Most patients with T2DM suffer serious complications due to chronic hyperglycemia, including nephropathy, neuropathy, retinopathy and accelerated development of cardiovascular disease.The prevalence of type 2 diabetes is continuing to increase in many countries, including Japan [4,5]. Clinical and epidemiological studies have indicated that obesity is a major risk factor for T2DM, because obesity is associated with an increased risk of developing insulin resistance and impaired glucose tolerance [6,7]. When β-cells are no longer able to secrete sufficient amounts of insulin to overcome insulin resistance, impaired glucose tolerance progresses to T2DM [7].The prevalence of obesity is also increasing worldwide, although there are large ethnic differences in the degree of obesity reached. In Japan, the prevalence of severe obesity (BMI ≥ 30 kg/m2) is lower than that in Western countries, where the prevalence of overweight (25 ≤ BMI < 30) adults has been steadi

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