Genetic associations with diabetes: meta-analyses of 10 candidate polymorphisms

Linlin Tang; Lingyan Wang; Qi Liao; Qinwen Wang; Leiting Xu; Shizhong Bu; Yi Huang; Cheng Zhang; Huadan Ye; Xuting Xu; Qiong Liu; Meng Ye; Yifeng Mai; Shiwei Duan

doi:10.1371/journal.pone.0070301

Genetic associations with diabetes: meta-analyses of 10 candidate polymorphisms

PLoS One. 2013 Jul 29;8(7):e70301. doi: 10.1371/journal.pone.0070301. Print 2013.

Authors

Linlin Tang¹, Lingyan Wang, Qi Liao, Qinwen Wang, Leiting Xu, Shizhong Bu, Yi Huang, Cheng Zhang, Huadan Ye, Xuting Xu, Qiong Liu, Meng Ye, Yifeng Mai, Shiwei Duan

Affiliation

¹ Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.

Abstract

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.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Diabetes Mellitus / genetics*
Diabetes Mellitus, Type 1 / genetics
Diabetes Mellitus, Type 2 / genetics
Genetic Predisposition to Disease*
Humans
Odds Ratio
Polymorphism, Genetic*
Polymorphism, Single Nucleotide

Grants and funding

The research was supported by the grants from National Natural Science Foundation of China (No. 31100919), Ningbo social development research projects(2012C50032), K.C. Wong Magna Fund in Ningbo University, Natural Science Foundation of Ningbo (2007A610077), and Program for Innovative Research Team in Zhejiang Province (2010R50046). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.