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

PLoS One. 2013;8(1):e54259. doi: 10.1371/journal.pone.0054259. Epub 2013 Jan 24.


Background: Some 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).

Methods: 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 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.

Results: In 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.

Conclusions: In 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.

Publication types

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

MeSH terms

  • Aged
  • Alleles
  • Asian People*
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / ethnology
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Gene Frequency
  • Genes, Dominant
  • Genes, Recessive
  • Genetic Predisposition to Disease*
  • Humans
  • Ion Channels / genetics*
  • Male
  • Middle Aged
  • Mitochondrial Proteins / genetics*
  • Odds Ratio
  • Polymorphism, Genetic*
  • Uncoupling Protein 1
  • Uncoupling Protein 2
  • Uncoupling Protein 3
  • White People*


  • Ion Channels
  • Mitochondrial Proteins
  • UCP1 protein, human
  • UCP2 protein, human
  • UCP3 protein, human
  • Uncoupling Protein 1
  • Uncoupling Protein 2
  • Uncoupling Protein 3

Grants and funding

This study was partially supported by grants from the Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS), the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and the Fundo de Incentivo à Pesquisa e Eventos (FIPE) at the Hospital de Clínicas de Porto Alegre. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.