Ethnicity Differences in the Association of UCP1-3826A/G, UCP2-866G/A and Ala55Val, and UCP3-55C/T Polymorphisms with Type 2 Diabetes Mellitus Susceptibility: An Updated Meta-Analysis

Abstract

Background. The relationship between uncoupling protein (UCP) 1-3 polymorphisms and susceptibility to type 2 diabetes mellitus (T2DM) has been extensively studied, while conclusions remain contradictory. Thus, we performed this meta-analysis to elucidate whether the UCP1-3826A/G, UCP2-866G/A, Ala55Val, and UCP3-55C/T polymorphisms are associated with T2DM. Methods. Eligible studies were searched from PubMed, Cochrane Library, and Web of Science database before 12 July 2020. Pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated to evaluate the strength of the association. Heterogeneity analysis, subgroup analysis, sensitivity analysis, and publication bias were also performed. Results. A total of 38 case-control studies were included in this meta-analysis. The overall results revealed significant association between T2DM and the UCP2 Ala55Val polymorphism (recessive model: $\text{OR}=1.25$ , 95% CI 1.12-1.40, $P<0.01$ ; homozygous model: $\text{OR}=1.33$ , 95% CI 1.03-1.72, $P=0.029$ , respectively). In subgroup analysis stratified by ethnicity, T2DM risk was increased with the UCP2 Ala55Val polymorphism (allele model: $\text{OR}=1.17$ , 95% CI 1.02-1.34, $P=0.023$ ; recessive model: $\text{OR}=1.28$ , 95% CI 1.13-1.45, $P<0.01$ ; homozygous model: $\text{OR}=1.39$ , 95% CI 1.05-1.86, $P=0.023$ , respectively), while decreased with the UCP2-866G/A polymorphism in Asians (dominant model: $\text{OR}=0.86$ , 95% CI 0.74-1.00, $P=0.045$ ). Conclusions. Our results demonstrate that the UCP2-866G/A polymorphism is protective against T2DM, while the UCP2 Ala55Val polymorphism is susceptible to T2DM in Asians.