Associations between UCP1 -3826A/G, UCP2 -866G/A, Ala55Val and Ins/Del, and UCP3 -55C/T Polymorphisms and Susceptibility to Type 2 Diabetes Mellitus: Case-Control Study and Meta-Analysis

Abstract

BackgroundSome studies have reported associations between five uncoupling protein (UCP) 1–3 polymorphisms and type 2 diabetes mellitus (T2DM). However, other studies have failed to confirm the associations. This paper describes a case-control study and a meta-analysis conducted to attempt to determine whether the following polymorphisms are associated with T2DM: -3826A/G (UCP1); -866G/A, Ala55Val and Ins/Del (UCP2) and -55C/T (UCP3).MethodsThe case-control study enrolled 981 T2DM patients and 534 nondiabetic subjects, all of European ancestry. A literature search was run to identify all studies that investigated associations between UCP1–3 polymorphisms and T2DM. Pooled odds ratios (OR) were calculated for allele contrast, additive, recessive, dominant and co-dominant inheritance models. Sensitivity analyses were performed after stratification by ethnicity.ResultsIn the case-control study the frequencies of the UCP polymorphisms did not differ significantly between T2DM and nondiabetic groups (P>0.05). Twenty-three studies were eligible for the meta-analysis. Meta-analysis results showed that the Ala55Val polymorphism was associated with T2DM under a dominant model (OR = 1.27, 95% CI 1.03–1.57); while the -55C/T polymorphism was associated with this disease in almost all genetic models: allele contrast (OR = 1.17, 95% CI 1.02–1.34), additive (OR = 1.32, 95% CI 1.01–1.72) and dominant (OR = 1.18, 95% CI 1.02–1.37). However, after stratification by ethnicity, the UCP2 55Val and UCP3 -55C/T alleles remained associated with T2DM only in Asians (OR = 1.25, 95% CI 1.02–1.51 and OR = 1.22, 95% CI 1.04–1.44, respectively; allele contrast model). No significant association of the -3826A/G, -866G/A and Ins/Del polymorphisms with T2DM was observed.ConclusionsIn our case-control study of people with European ancestry we were not able to demonstrate any association between the UCP polymorphisms and T2DM; however, our meta-analysis detected a significant association between the UCP2 Ala55Val and UCP3 -55C/T polymorphisms and increased susceptibility for T2DM in Asians.

Interactions between uncoupling protein 2 gene polymorphisms, obesity and alcohol intake on liver function: a large meta-analysed population-based study

“…These polymorphisms have been shown to be associated with various metabolic traits such as obesity (24), body fat distribution (25), resting energy expenditure (26), type 2 diabetes (10) and insulin resistance (9,27) in various populations from different ethnic backgrounds (24). However, there were also studies that failed to show an association between these polymorphisms and metabolic traits (8,28,29). These inconsistencies could be attributed to the small sample size, incomplete coverage of the UCP2 gene variations or potential population-specific influences on metabolic traits (29).…”

“…However, there were also studies that failed to show an association between these polymorphisms and metabolic traits (8,28,29). These inconsistencies could be attributed to the small sample size, incomplete coverage of the UCP2 gene variations or potential population-specific influences on metabolic traits (29). Hence, in our study we have performed a meta-analysis of data from three large European cohorts (n up to 20 242) and used the tagSNP approach to capture all common genetic variations within the UCP2 gene.…”

Association between Asp299Gly and Thr399Ile Polymorphisms in Toll-Like Receptor 4 Gene and Type 2 Diabetes Mellitus: Case-Control Study and Meta- Analysis

“…Articles were excluded from the analysis if the genotype frequencies in the control group deviated from those predicted by the HWE and if they did not have enough data to estimate an OR with 95% CI. If data were duplicated and had been published more than once, the most complete study was chosen [25,26,33,34].…”

Association between Asp299Gly and Thr399Ile Polymorphisms in Toll-Like Receptor 4 Gene and Type 2 Diabetes Mellitus: Case-Control Study and Meta-Analysis

“…Other inheritance models were not analyzed due to the rarity of the minor alleles. Heterogeneity was tested using χ²-based Cochran's Q statistic and inconsistency was assessed with the I² metric, as previously described [25,26,33,34]. Briefly, heterogeneity was considered statistically significant at P <0.10 for the Q statistic and I²>50% for the I² metric statistics.…”

“…for the pooled effect; where heterogeneity was not significant, the fixed effect model (FEM) was used for this evaluation [37]. Meta-regression and sensitivity analyses were performed to identify important studies with a significant impact on inter-study heterogeneity [25,26,33,34]. The factors investigated by meta-regression were age, BMI and gender.…”