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

<div><h3>Background</h3><p>Some studies have reported associations between five uncoupling protein (<em>UCP</em>) <em>1–3</em> 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 (<em>UCP1</em>); -866G/A, Ala55Val and Ins/Del (<em>UCP2</em>) and -55C/T (<em>UCP3</em>).</p> <h3>Methods</h3><p>The 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 <em>UCP1–3</em> 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.</p> <h3>Results</h3><p>In the case-control study the frequencies of the <em>UCP</em> 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 <em>UCP2</em> 55Val and <em>UCP3</em> -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.</p> <h3>Conclusions</h3><p>In our case-control study of people with European ancestry we were not able to demonstrate any association between the <em>UCP</em> polymorphisms and T2DM; however, our meta-analysis detected a significant association between the <em>UCP2</em> Ala55Val and <em>UCP3</em> -55C/T polymorphisms and increased susceptibility for T2DM in Asians.</p> </div>