Department of Endocrinology and Metabolism, Peking University People's Hospital, Peking University Diabetes Center, No 11, Xizhimen South Street, Beijing, China.
BMC Med Genet. 2010 May 28;11:81. doi: 10.1186/1471-2350-11-81.
Recently, several genome-wide and candidate gene association studies have identified many novel genetic loci for type 2 diabetes (T2D); among these genes, CDKAL1, IGF2BP2, SLC30A8, CDKN2A/B, HHEX, FTO, TCF2, KCNQ1, and WFS1 are the most important. We aimed to determine the effects of these genetic loci associated with T2D in the Chinese Han population of China.
Single-nucleotide polymorphisms (SNPs) in or near CDKAL1, IGF2BP2, SLC30A8, CDKN2A/B, HHEX, FTO, TCF2, KCNQ1, and WFS1 genes were genotyped in a case-control Chinese Han sample living in Beijing, China involving 1024 patients with T2D and 1005 control subjects.
In Chinese Han, we replicated the associations between 7 genetic loci and T2D, with risk allele-specific odds ratios (ORs) as follows: 1.27 (95% CI, 1.11-1.45; p = 0.0008) for CDKAL1-rs10946398, 1.26 (95% CI, 1.08-1.47; p = 0.003) for IGF2BP2-rs4402960, 1.19 (95% CI, 1.04-1.37; p = 0.009) for SLC30A8-rs13266634, 1.22 (95% CI, 1.06-1.41; p = 0.005) for CDKN2A/B-rs10811661, 1.20 (95% CI, 1.01-1.42; p = 0.03) for HHEX-rs5015480, 1.37 (95% CI, 1.19-1.69; p = 1.0 x 10(-4)) for KCNQ1-rs2237892, and 1.24 (95% CI, 1.01-1.52; p = 0.046) for FTO-rs8050136 after adjustment for age, gender, and body mass index. Not only did an association between WFS1-rs6446482 and early-onset T2D exist in the subgroup analysis, but TCF2-rs7501939 and WFS1-rs6446482 were also confirmed to confer risk for T2D in this meta-analysis. Moreover, the relationship between FTO-rs8050136 and body mass index, together with the effect of CDKAL1-rs10946398 on beta cell function, was also observed in the control individuals.
Our findings support the important contribution of these genetic loci to susceptibility for T2D in the Chinese Han population in Beijing of China.
最近，几项全基因组和候选基因关联研究已经确定了许多新的 2 型糖尿病（T2D）遗传位点；在这些基因中，CDKAL1、IGF2BP2、SLC30A8、CDKN2A/B、HHEX、FTO、TCF2、KCNQ1 和 WFS1 是最重要的。我们旨在确定这些与中国汉族人群 T2D 相关的遗传位点的影响。
在中国北京的汉族病例对照样本中，对 CDKAL1、IGF2BP2、SLC30A8、CDKN2A/B、HHEX、FTO、TCF2、KCNQ1 和 WFS1 基因内或附近的单核苷酸多态性（SNP）进行基因分型，涉及 1024 例 T2D 患者和 1005 例对照。
在中国汉族人群中，我们复制了 7 个遗传位点与 T2D 的关联，风险等位基因特异性优势比（OR）如下：CDKAL1-rs10946398 为 1.27（95%CI，1.11-1.45；p=0.0008），IGF2BP2-rs4402960 为 1.26（95%CI，1.08-1.47；p=0.003），SLC30A8-rs13266634 为 1.19（95%CI，1.04-1.37；p=0.009），CDKN2A/B-rs10811661 为 1.22（95%CI，1.06-1.41；p=0.005），HHEX-rs5015480 为 1.20（95%CI，1.01-1.42；p=0.03），KCNQ1-rs2237892 为 1.37（95%CI，1.19-1.69；p=1.0×10(-4))，FTO-rs8050136 为 1.24（95%CI，1.01-1.52；p=0.046），经年龄、性别和体重指数调整后。WFS1-rs6446482 与早发性 T2D 的关联不仅在亚组分析中存在，而且 TCF2-rs7501939 和 WFS1-rs6446482 也在本荟萃分析中被证实与 T2D 相关。此外，还观察到 FTO-rs8050136 与体重指数之间的关系，以及 CDKAL1-rs10946398 对胰岛β细胞功能的影响，在对照个体中也存在。
我们的研究结果支持这些遗传位点在中国北京汉族人群中对 T2D 易感性的重要贡献。
