Dataset Information

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: OR = 1.25, 95% CI 1.12-1.40, P < 0.01; homozygous model: 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: OR = 1.17, 95% CI 1.02-1.34, P = 0.023; recessive model: OR = 1.28, 95% CI 1.13-1.45, P < 0.01; homozygous model: 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: 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.

SUBMITTER: Huang R

PROVIDER: S-EPMC8548105 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Aims/hypothesisVariants of UCP2 and UCP3 genes have been reported to be associated with obesity, but the available data on the relationship are inconsistent. A meta-analysis was performed to determine whether there are any associations between the UCP2 -866G/A, Ala55Val, and UCP3 -55C/T polymorphisms and obesity susceptibility.MethodsThe PubMed, Embase, Web of Science and CNKI, CBMdisc databases were searched for all relevant case-control studies. The fixed or random effect pooled measure was determined on the bias of heterogeneity test among studies. Publication bias was examined by the modified Begg's and Egger's test.ResultsTwenty-two published articles with thirty-two outcomes were included in the meta-analysis: 12 studies with a total of 7,390 cases and 9,860 controls were analyzed for UCP2 -866G/A polymorphism with obesity, 9 studies with 1,483 cases and 2,067 controls for UCP2 Ala55Val and 8 studies with 2,180 cases and 2,514 controls for UCP3 -55C/T polymorphism. Using an additive model, the UCP2 -866G/A polymorphism showed no significant association with obesity risk in Asians (REM OR = 0.81, 95% CI: 0.65-1.01). In contrast, a statistically significant association was observed in subjects of European descent (FEM OR = 1.06, 95% CI: 1.01-1.12). But neither the UCP2 Ala55Val nor the UCP3 -55C/T polymorphism showed any significant association with obesity risk in either subjects of Asian (REM OR = 0.84, 95% CI: 0.67-1.06 for Ala55Val; REM OR = 0.94, 95% CI: 0.55-1.28 for -55C/T) or of European descent (REM OR = 1.04, 95% CI: 0.80-1.36 for Ala55Val; FEM OR = 1.08, 95% CI: 0.97-1.20 for -55C/T).Conclusions and interpretationOur meta-analysis revealed that the UCP2 -866G/A polymorphism may be a risk factor for susceptibility to obesity in subjects of European descent, but not in individuals of Asian descent. And our results did not support the association between UCP2 Ala55Val, UCP3 -55C/T polymorphisms and obesity in the populations investigated. This conclusion warrants confirmation by further studies.

Project description: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.

Project description:Abstract Background: The uncoupling proteins (UCPs) belong to the mitochondrial inner membrane anion carrier superfamily and play an important role in energy homeostasis. UCP-1 is expressed mostly in brown adipose tissue (BAT) and act in the thermogenesis and regulation of energy expenditure. UCP-2 has a role in the metabolism of fatty acids direct and indirectly path insulin secretion. UCP-3 is specific of skeletal muscle and BAT and may affects the adaptive and translocation of fatty acids. Genetic polymorphisms in these proteins have been associated with obesity, as rs1800592 (-3826 A/G) in UCP-1 gene. The rs659366 (-866GA) UCP-2 has being associated with high expression of its RNAm, decrease of obesity risk, and increase of energy expenditure. The rs1800849 (-55CT) UCP-3 has been associated with low risk of type 2 Diabetes Mellitus, but its association with body mass index is controversial. Objective: To analyze the association of the polymorphisms rs1800592 UCP-1, rs659366 UCP-2, and rs1800849 UCP-3 with BMI and resting energy expenditure (REE). Material and Methods: We included 120 subjects with BMI>30kg/m2 and 100 subjects with BMI between18.5 -24.9 kg/m2, aged 20 to 50 years. Anthropometric data were recorded and the REE was measure for indirect calorimetric. Fasting glucose and lipid profile were assessed. Leptin, insulin and acylated-ghrelin were quantified by ELISA. Genomic DNA was extracted using comercial kit. Genotyping for three polymorphisms was performed by allelic discrimination using Taqman probes. Results: All the three polymorphisms of UCPs showed distribution in accordance with Hardy-Weinberg equilibrium. The weight, BMI, glucose, triglycerides, leptin, insulin, HOMA-IR, and REE levels were signitifcantly higher in obese subjects. There was a strong correlation between REE with BMI (r=0.42, p<0.00001) and with insulin levels (r=0.229, p=0.001) in all group. No differences in genotypic and allelic frequencies of rs1800592 UCP-1, rs659366 UCP-2 and rs180084 UCP-3 polymorphisms between obese and lean subjects. No differences among the genotypes rs1800592 UCP-1 and rs1800849 UCP-3 with metabolic variables. In rs659366 UCP-2 polymorhism, the REE and glucose concentrations were lower in carriers of rs659366AA genotype (F=3.11, p=0.046; F=2.97, p=0.053, respectively) in whole group. In obese subjects with rs659366AA UCP-2 genotype, the REE was significantly low (F=4.15, P=0.017). Conclusion. In this work the obese subjects with rs659366AA genotype had low REE. We found low glucose concentrations in the carries of rs659366 AA genotype.