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      Uncoupling protein 2 gene polymorphisms in association with overweight and obesity susceptibility: A meta-analysis

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          Abstract

          A meta-analysis was performed to evaluate the associations of uncoupling protein 2 ( UCP2) gene polymorphisms (Ala55Val, 45-bp insertion/deletion, and -866G/A) with overweight and obesity. A total of 42 studies were included in our analysis. Pooled effect estimates and 95% confidential intervals of each polymorphism were calculated under different inherited models. Fixed or random effect model was selected based on the between-study heterogeneity evaluated with I 2 . Source of heterogeneity was explored by subgroup analysis and meta-regression analysis. Potential publication bias was assessed using funnel plot and Peters test. After excluding studies that deviated from the Hardy–Weinberg equilibrium, T allele of Ala55Val polymorphism was associated with an increased risk of overweight and obesity under recessive model in the overall (OR = 1.24, 95%CI = 1.06–1.45) and Asian (OR = 1.28, 95%CI = 1.06–1.55) populations; and A allele of -866G/A polymorphism had a protective effect on overweight and obesity, especially for European populations (dominant model: OR = 0.88, 95%CI = 0.81–0.96, co-dominant 1 model: OR = 0.89, 95%CI = 0.81–0.98, co-dominant 2 model: OR = 0.85, 95%CI = 0.74–0.94, additive model: OR = 0.88, 95%CI = 0.80–0.95, and allelic model: OR = 0.91, 95%CI = 0.86–0.97). No evidence was observed in the association of 45-bp insertion/deletion polymorphism with overweight and obesity susceptibility. We failed to fully explore the between-study heterogeneity regarding the association of Ala55Val polymorphism with overweight and obesity. Further studies are required to provide more convincing evidence.

          Highlights

          • We evaluated the association of UCP2 gene polymorphisms with overweight and obesity.

          • Ala55Val polymorphism was associated with an increased risk in Asian populations.

          • No association was observed for 45-bp insertion/deletion polymorphism.

          • -866G/A polymorphism was associated with a decreased risk in European populations.

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          Most cited references40

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          Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia.

          A mitochondrial protein called uncoupling protein (UCP1) plays an important role in generating heat and burning calories by creating a pathway that allows dissipation of the proton electrochemical gradient across the inner mitochondrial membrane in brown adipose tissue, without coupling to any other energy-consuming process. This pathway has been implicated in the regulation of body temperature, body composition and glucose metabolism. However, UCP1-containing brown adipose tissue is unlikely to be involved in weight regulation in adult large-size animals and humans living in a thermoneutral environment (one where an animal does not have to increase oxygen consumption or energy expenditure to lose or gain heat to maintain body temperature), as there is little brown adipose tissue present. We now report the discovery of a gene that codes for a novel uncoupling protein, designated UCP2, which has 59% amino-acid identity to UCP1, and describe properties consistent with a role in diabetes and obesity. In comparison with UCP1, UCP2 has a greater effect on mitochondrial membrane potential when expressed in yeast. Compared to UCP1, the gene is widely expressed in adult human tissues, including tissues rich in macrophages, and it is upregulated in white fat in response to fat feeding. Finally, UCP2 maps to regions of human chromosome 11 and mouse chromosome 7 that have been linked to hyperinsulinaemia and obesity. Our findings suggest that UCP2 has a unique role in energy balance, body weight regulation and thermoregulation and their responses to inflammatory stimuli.
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            Meta-analysis of genetic association studies.

            Meta-analysis, a statistical tool for combining results across studies, is becoming popular as a method for resolving discrepancies in genetic association studies. Persistent difficulties in obtaining robust, replicable results in genetic association studies are almost certainly because genetic effects are small, requiring studies with many thousands of subjects to be detected. In this article, we describe how meta-analysis works and consider whether it will solve the problem of underpowered studies or whether it is another affliction visited by statisticians on geneticists. We show that meta-analysis has been successful in revealing unexpected sources of heterogeneity, such as publication bias. If heterogeneity is adequately recognized and taken into account, meta-analysis can confirm the involvement of a genetic variant, but it is not a substitute for an adequately powered primary study.
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              Mitochondrial uncoupling protein 2 (UCP2) in glucose and lipid metabolism.

              Nutrient availability is critical for the physiological functions of all tissues. By contrast, an excess of nutrients such as carbohydrate and fats impair health and shorten life due by stimulating chronic diseases, including diabetes, cancer and neurodegeneration. The control of circulating glucose and lipid levels involve mitochondria in both central and peripheral mechanisms of metabolism regulation. Mitochondrial uncoupling protein 2 (UCP2) has been implicated in physiological and pathological processes related to glucose and lipid metabolism, and in this review we discuss the latest data on the relationships between UCP2 and glucose and lipid sensing from the perspective of specific hypothalamic neuronal circuits and peripheral tissue functions. The goal is to provide a framework for discussion of future therapeutic strategies for metabolism-related chronic diseases. Copyright © 2011 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Meta Gene
                Meta Gene
                Meta Gene
                Elsevier
                2214-5400
                31 January 2014
                December 2014
                31 January 2014
                : 2
                : 143-159
                Affiliations
                Department of Epidemiology and Health Statistics, School of Public Health, Shandong University, 44 Wenhua Xi Road, Ji'nan, Shandong 250012, China
                Author notes
                [* ]Corresponding author at: Department of Epidemiology and Health Statistics, Shandong University, No. 44 Wenhua Xi Road, Ji'nan 250012, China. Tel./fax: + 86 531 88382128. ztzhao@ 123456sdu.edu.cn
                Article
                S2214-5400(13)00021-2
                10.1016/j.mgene.2013.10.009
                4287797
                25606398
                dfd603f0-e91c-4b97-a2b0-d654dfb2b4bd
                © 2013 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

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                ucp, uncoupling protein,or, odds ratio,ci, confidence interval,rem, random effect model,fem, fixed effect model,hwe, hardy–weinberg equilibrium,obesity,adiposity,uncoupling protein,polymorphism,meta-analysis

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