与糖尿病相关的遗传关联：10 个候选多态性的荟萃分析。
Genetic associations with diabetes: meta-analyses of 10 candidate polymorphisms.
机构信息
Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
出版信息
PLoS One. 2013 Jul 29;8(7):e70301. doi: 10.1371/journal.pone.0070301. Print 2013.
AIMS
The goal of our study is to investigate the combined contribution of 10 genetic variants to diabetes susceptibility.
METHODS
Bibliographic databases were searched from 1970 to Dec 2012 for studies that reported on genetic association study of diabetes. After a comprehensive filtering procedure, 10 candidate gene variants with informative genotype information were collected for the current meta-anlayses. Using the REVMAN software, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the combined contribution of the selected genetic variants to diabetes.
RESULTS
A total of 37 articles among 37,033 cases and 54,716 controls were involved in the present meta-analyses of 10 genetic variants. Three variants were found to be significantly associated with type 1 diabetes (T1D): NLRP1 rs12150220 (OR = 0.71, 95% CI = 0.55-0.92, P = 0.01), IL2RA rs11594656 (OR = 0.86, 95% CI = 0.82-0.91, P<0.00001), and CLEC16A rs725613 (OR = 0.71, 95% CI = 0.55-0.92, P = 0.01). APOA5 -1131T/C polymorphism was shown to be significantly associated with of type 2 diabetes (T2D, OR = 1.27, 95% CI = 1.03-1.57, P = 0.03). No association with diabetes was showed in the meta-analyses of other six genetic variants, including SLC2A10 rs2335491, ATF6 rs2070150, KLF11 rs35927125, CASQ1 rs2275703, GNB3 C825T, and IL12B 1188A/C.
CONCLUSION
Our results demonstrated that IL2RA rs11594656 and CLEC16A rs725613 are protective factors of T1D, while NLRP1 rs12150220 and APOA5 -1131T/C are risky factors of T1D and T2D, respectively.
目的
我们的研究目的是探讨 10 个遗传变异对糖尿病易感性的联合贡献。
方法
从 1970 年至 2012 年 12 月，我们检索了文献数据库，以寻找报告糖尿病遗传关联研究的研究。经过全面的筛选程序，我们收集了 10 个具有信息基因型的候选基因变异体，用于当前的荟萃分析。使用 REVMAN 软件，计算比值比（OR）及其 95%置信区间（CI），以评估所选遗传变异对糖尿病的综合贡献。
结果
在对 10 个遗传变异体的荟萃分析中，共有 37 篇文章纳入了 37033 例病例和 54716 例对照。有 3 个变异体与 1 型糖尿病（T1D）显著相关：NLRP1 rs12150220（OR=0.71，95%CI=0.55-0.92，P=0.01），IL2RA rs11594656（OR=0.86，95%CI=0.82-0.91，P<0.00001）和 CLEC16A rs725613（OR=0.71，95%CI=0.55-0.92，P=0.01）。APOA5-1131T/C 多态性与 2 型糖尿病（T2D，OR=1.27，95%CI=1.03-1.57，P=0.03）显著相关。在对其他 6 个遗传变异体的荟萃分析中，没有发现与糖尿病相关的关联，包括 SLC2A10 rs2335491、ATF6 rs2070150、KLF11 rs35927125、CASQ1 rs2275703、GNB3 C825T 和 IL12B 1188A/C。
结论
我们的研究结果表明，IL2RA rs11594656 和 CLEC16A rs725613 是 T1D 的保护因素，而 NLRP1 rs12150220 和 APOA5-1131T/C 分别是 T1D 和 T2D 的风险因素。
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