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.
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.
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DOI：
10.1186/1471-2350-13-11
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发表时间：
2012-02-24
影响因子：
--
通讯作者：
Goda T
中科院分区：
文献类型：
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作者：
Yamakawa-Kobayashi K;Natsume M;Aoki S;Nakano S;Inamori T;Kasezawa N;Goda T
2 型糖尿病（T2DM）是一种复杂的内分泌和代谢疾病。最近，多项全基因组关联研究（GWAS）发现了许多新的 T2DM 易感位点，并表明全球多个人群中存在共同的遗传原因导致 T2DM 易感性。此外，临床和流行病学研究表明，肥胖是T2DM的主要危险因素。然而，不同种族群体的肥胖患病率有所不同。我们的目的是确定这些易感位点和肥胖/超重对日本人发生 T2DM 的综合影响。通过 GWAS 在白人和亚洲人群中鉴定出 17 个 T2DM 易感位点内或附近的单核苷酸多态性 (SNP)，并在 333 名 T2DM 病例和 417 名对照受试者中进行了基因分型。我们证实，基于 17 个 T2DM 易感位点的风险等位基因的累积数量是日本人群发生 T2DM 的重要危险因素（P < 0.0001），尽管每个风险等位基因的影响相对较小。此外，在非肥胖组中观察到风险等位基因数量增加与 T2DM 风险增加之间存在显着关联（趋势 P < 0.0001），但在肥胖/超重组中则没有观察到（趋势 P = 0.88）。我们的研究结果表明，肥胖/超重和非肥胖受试者之间的 T2DM 病因存在异质性。
Type 2 diabetes mellitus (T2DM) is a complex endocrine and metabolic disorder. Recently, several genome-wide association studies (GWAS) have identified many novel susceptibility loci for T2DM, and indicated that there are common genetic causes contributing to the susceptibility to T2DM in multiple populations worldwide. In addition, clinical and epidemiological studies have indicated that obesity is a major risk factor for T2DM. However, the prevalence of obesity varies among the various ethnic groups. We aimed to determine the combined effects of these susceptibility loci and obesity/overweight for development of T2DM in the Japanese. 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.