Laboratory for Endocrinology and Metabolism, RIKEN Center for Genomic Medicine, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
Diabetologia. 2011 Dec;54(12):3071-7. doi: 10.1007/s00125-011-2293-3. Epub 2011 Sep 10.
AIMS/HYPOTHESIS: Recently, rs10906115 in CDC123/CAMK1D, rs1359790 near SPRY2, rs1436955 in C2CD4A/C2CD4B and rs10751301 in ODZ4 were identified as genetic risk variants for type 2 diabetes by a genome-wide association study in a Chinese population. The aim of the present study was to ascertain the role of these four variants in conferring susceptibility to type 2 diabetes in the Japanese population.
We genotyped 11,530 Japanese individuals (8,552 type 2 diabetes cases, 2,978 controls) for the above single nucleotide polymorphisms (SNPs) and used logistic regression analysis to determine whether they were associated with type 2 diabetes.
In accordance with the findings in a Chinese population, rs10906115 A, rs1359790 C and rs1436955 G were found to be risk alleles. Both rs10906115 and rs1359790 were significantly associated with susceptibility to type 2 diabetes in our study (rs10906115 OR 1.15, 95% CI 1.08, 1.22; p = 6.10 × 10(-6); rs1359790 OR 1.14, 95% CI 1.06, 1.21; p = 2.24 × 10(-4)). Adjustment for age, sex and BMI had no significant effects on the association between these variants and the disease. We did not observe any significant associations between the SNPs and any metabolic traits, e.g. BMI, fasting plasma glucose (determined for 1,332 controls), HOMA of beta cell function (900 controls) and HOMA of insulin resistance (900 controls; p > 0.05).
CONCLUSIONS/INTERPRETATION: The SNPs rs10906115 A and rs1359790 C are significantly associated with susceptibility to type 2 diabetes in the Japanese population, confirming that these alleles are common susceptibility variants for type 2 diabetes in East Asian populations.
目的/假设:最近,在一项中国人群的全基因组关联研究中,rs10906115 位于 CDC123/CAMK1D 基因内,rs1359790 位于 SPRY2 附近,rs1436955 位于 C2CD4A/C2CD4B 基因内,rs10751301 位于 ODZ4 基因内,被鉴定为 2 型糖尿病的遗传风险变异。本研究的目的是确定这四个变异在日本人群中对 2 型糖尿病易感性的作用。
我们对 11530 名日本人(8552 例 2 型糖尿病患者,2978 例对照)进行了上述单核苷酸多态性(SNP)的基因分型,并使用逻辑回归分析确定它们是否与 2 型糖尿病相关。
与中国人群的研究结果一致,我们发现 rs10906115A、rs1359790C 和 rs1436955G 是风险等位基因。rs10906115 和 rs1359790 在我们的研究中均与 2 型糖尿病易感性显著相关(rs10906115 OR 1.15,95%CI 1.08,1.22;p=6.10×10(-6);rs1359790 OR 1.14,95%CI 1.06,1.21;p=2.24×10(-4))。调整年龄、性别和 BMI 对这些变异与疾病之间的关联没有显著影响。我们没有观察到 SNP 与任何代谢特征之间存在任何显著关联,例如 BMI、空腹血糖(对 1332 名对照者进行测定)、β细胞功能的 HOMA(900 名对照者)和胰岛素抵抗的 HOMA(900 名对照者;p>0.05)。
结论/解释:在日本人群中,SNP rs10906115A 和 rs1359790C 与 2 型糖尿病易感性显著相关,证实这些等位基因是东亚人群 2 型糖尿病的常见易感变异。