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 | 2021

REPOSITORIES: biostudies-literature

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Publications

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.

Huang Rong R Cai Tingting T Zhou Yunting Y Wang Yuming Y Wang Huiying H Shen Ziyang Z Xia Wenqing W Liu Xiaomei X Ding Bo B Luo Yong Y Yan Rengna R Li Huiqin H Wu Jindan J Ma Jianhua J

BioMed research international 20211019

<h4>Background</h4>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.<h4>Methods</h4>Eligible studies were searched from PubMed, Cochrane Library, and Web of Science database before 12 July 2020. Pooled o ...[more]

PMID: 34712730

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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.

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.

Background

Methods

Results

Conclusions

Publications

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.

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