It is well established that genetic factors play an important role in the development of both type 2 diabetes mellitus (DM2) and obesity, and that genetically susceptible subjects can develop these metabolic diseases after being exposed to environmental risk factors. Therefore, great efforts have been made to identify genes associated with DM2 and/or obesity. Uncoupling protein 1 (UCP1) is mainly expressed in brown adipose tissue, and acts in thermogenesis, regulation of energy expenditure, and protection against oxidative stress. All these mechanisms are associated with the pathogenesis of DM2 and obesity. Hence, UCP1 is a candidate gene for the development of these disorders. Indeed, several studies have reported that polymorphisms -3826A/G, -1766A/G and -112A/C in the promoter region, Ala64Thr in exon 2 and Met299Leu in exon 5 of UCP1 gene are possibly associated with obesity and/or DM2. However, results are still controversial in different populations. Thus, the aim of this study was to review the role of UCP1 in the development of these metabolic diseases.

BackgroundThe relationship between uncoupling protein (UCP) 1–3 polymorphisms and susceptibility to obesity has been investigated in several genetic studies. However, the impact of these polymorphisms on obesity is still under debate, with contradictory results being reported. Until this date, no meta-analysis evaluated the association of UCP polymorphisms with body mass index (BMI) variability. Thus, this paper describe a meta-analysis conducted to evaluate if the -3826A/G (UCP1); -866G/A, Ala55Val and Ins/Del (UCP2) and -55C/T (UCP3) polymorphisms are associated with BMI changes.MethodsA literature search was run to identify all studies that investigated associations between UCP1-3 polymorphisms and BMI. Weighted mean differences (WMD) were calculated for different inheritance models.ResultsFifty-six studies were eligible for inclusion in the meta-analysis. Meta-analysis results showed that UCP2 55Val/Val genotype was associated with increased BMI in Europeans [Random Effect Model (REM) WMD 0.81, 95% CI 0.20, 1.41]. Moreover, the UCP2 Ins allele and UCP3-55T/T genotype were associated with increased BMI in Asians [REM WMD 0.46, 95% CI 0.09, 0.83 and Fixed Effect Model (FEM) WMD 1.63, 95% CI 0.25, 3.01]. However, a decreased BMI mean was observed for the UCP2-866 A allele in Europeans under a dominant model of inheritance (REM WMD −0.18, 95% CI −0.35, −0.01). There was no significant association of the UCP1-3826A/G polymorphism with BMI mean differences.ConclusionsThe meta-analysis detected a significant association between the UCP2-866G/A, Ins/Del, Ala55Val and UCP3-55C/T polymorphisms and BMI mean differences.

Introduction: Viral pathogens seem to play a role in triggering the autoimmune destruction that leads to the development of type 1 diabetes mellitus (T1DM). Toll-like receptor 3 (TLR3) has been shown to recognize double-stranded RNA, a molecular signature of most viruses. It is expressed at high levels in pancreatic b-cells and immune cells, suggesting a role for it in the pathogenesis of T1DM. Therefore, the aim of this study was to investigate whether TLR3 polymorphisms are associated with T1DM. Methods: Frequencies of the TLR3 rs11721827, rs13126816, rs5743313, rs7668666, and rs3775291 polymorphisms were analyzed in 449 T1DM patients and in 507 nondiabetic subjects. Haplotypes constructed from the combination of these polymorphisms were inferred using a Bayesian statistical method. Results: The rs3775291 and rs13126816 polymorphisms were associated with T1DM, and the strongest association was observed for the additive model (odds ratio (OR)Z2.3, 95% CI 1.3-4.2 and ORZ2.1, 95% CI 1.3-3.1 respectively). In the same way, the frequency of T1DM was higher as more risk alleles of the five polymorphisms were present (P-trendZ0.001). Moreover, in T1DM patients, the minor alleles of the rs5743313 and rs117221827 polymorphisms were associated with an early age at diagnosis and worse glycemic control. Conclusion: The TLR3 rs3775291 and rs13126816 polymorphisms are associated with risk for T1DM, while the rs5743313 and rs11721827 polymorphisms are associated with age at T1DM diagnosis and poor glycemic control. The number of risk alleles of the five TLR3 polymorphisms in the haplotypes seems to influence the risk for T1DM, suggesting that these polymorphisms might interact in the susceptibility for the disease.