Uncoupling Protein 2 Gene Polymorphisms in Association with Overweight and Obesity Susceptibility: A Meta-analysis

Overview

Journal Meta Gene

Publisher Elsevier

Specialty Genetics

Date 2015 Jan 22

PMID 25606398

Citations 14

Authors

Meng Zhang

Meng Wang

Zhong-Tang Zhao

Affiliations

Soon will be listed here.

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.

Citing Articles

"GENYAL" Study to Childhood Obesity Prevention: Methodology and Preliminary Results.

Marcos-Pasero H, Aguilar-Aguilar E, de la Iglesia R, Espinosa-Salinas I, Molina S, Colmenarejo G Front Nutr. 2022; 9:777384.

PMID: 35350411 PMC: 8957940. DOI: 10.3389/fnut.2022.777384.

Association of 45-bp ins/del polymorphism of uncoupling protein 2 (UCP2) and susceptibility to nonalcoholic fatty liver and type 2 diabetes mellitus in North-west of Iran.

Rezapour S, Ahdi Khosroshahi S, Farajnia H, Mohseni F, Khoshbaten M, Farajnia S BMC Res Notes. 2021; 14(1):169.

PMID: 33957975 PMC: 8101211. DOI: 10.1186/s13104-021-05586-9.

Association of uncoupling protein (Ucp) gene polymorphisms with cardiometabolic diseases.

Pravednikova A, Shevchenko S, Kerchev V, Skhirtladze M, Larina S, Kachaev Z Mol Med. 2020; 26(1):51.

PMID: 32450815 PMC: 7249395. DOI: 10.1186/s10020-020-00180-4.

The Interaction between Coffee: Caffeine Consumption, UCP2 Gene Variation, and Adiposity in Adults-A Cross-Sectional Study.

Muhammad H, Sulistyoningrum D, Huriyati E, Lee Y, Muda W J Nutr Metab. 2019; 2019:9606054.

PMID: 30719347 PMC: 6334331. DOI: 10.1155/2019/9606054.

Uncoupling Protein 2 (UCP2) as Genetic Risk Factor for Obesity in Indonesia is Different in Gender Stratification.

Surniyantoro H, Sadewa A, Hastuti P Kobe J Med Sci. 2018; 64(2):E64-E72.

PMID: 30381728 PMC: 6347053.

References

Liu L, Zhao X, Kang S, Zhang D . An association between -866G/A polymorphism in the promoter of UCP2 and obesity: a meta-analysis. Gene. 2012; 514(1):41-7. DOI: 10.1016/j.gene.2012.11.001. View

Sui Y, Weng J, Xiu L, Wang J, Yan J . [Additive effects of the variants in the beta(3)-adrenergic receptor and uncoupling protein-2 genes on obesity in Chinese]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2004; 21(3):229-32. View

Zhang C, Baffy G, Perret P, Krauss S, Peroni O, Grujic D . Uncoupling protein-2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction, and type 2 diabetes. Cell. 2001; 105(6):745-55. DOI: 10.1016/s0092-8674(01)00378-6. View

Andersen G, Dalgaard L, Justesen J, Anthonsen S, Nielsen T, Thorner L . The frequent UCP2 -866G>A polymorphism protects against insulin resistance and is associated with obesity: a study of obesity and related metabolic traits among 17 636 Danes. Int J Obes (Lond). 2012; 37(2):175-81. DOI: 10.1038/ijo.2012.22. View

Urhammer S, Dalgaard L, Sorensen T, Moller A, Andersen T, Tybjaerg-Hansen A . Mutational analysis of the coding region of the uncoupling protein 2 gene in obese NIDDM patients: impact of a common amino acid polymorphism on juvenile and maturity onset forms of obesity and insulin resistance. Diabetologia. 1998; 40(10):1227-30. DOI: 10.1007/s001250050811. View

Wang T, Huang M, Lin H, Hsiang C, Ko A, Chang W . UCP2 A55V variant is associated with obesity and related phenotypes in an aboriginal community in Taiwan. Int J Obes (Lond). 2007; 31(11):1746-52. DOI: 10.1038/sj.ijo.0803648. View

Higgins J, Thompson S . Quantifying heterogeneity in a meta-analysis. Stat Med. 2002; 21(11):1539-58. DOI: 10.1002/sim.1186. View

Ochoa M, Santos J, Azcona C, Moreno-Aliaga M, Martinez-Gonzalez M, Martinez J . Association between obesity and insulin resistance with UCP2-UCP3 gene variants in Spanish children and adolescents. Mol Genet Metab. 2007; 92(4):351-8. DOI: 10.1016/j.ymgme.2007.07.011. View

Schauble N, Geller F, Siegfried W, Goldschmidt H, Remschmidt H, Hinney A . No evidence for involvement of the promoter polymorphism -866 G/A of the UCP2 gene in childhood-onset obesity in humans. Exp Clin Endocrinol Diabetes. 2003; 111(2):73-6. DOI: 10.1055/s-2003-39232. View

10.

Yiew S, Khor L, Tan M, Pang C, Chai V, Kanachamy S . No association between peroxisome proliferator-activated receptor and uncoupling protein gene polymorphisms and obesity in Malaysian university students. Obes Res Clin Pract. 2013; 4(4):e247-342. DOI: 10.1016/j.orcp.2010.03.002. View

11.

Munafo M, Flint J . Meta-analysis of genetic association studies. Trends Genet. 2004; 20(9):439-44. DOI: 10.1016/j.tig.2004.06.014. View

12.

Fleury C, Neverova M, Collins S, Raimbault S, CHAMPIGNY O, Levi-Meyrueis C . Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. Nat Genet. 1997; 15(3):269-72. DOI: 10.1038/ng0397-269. View

13.

Kosuge K, Soma M, Nakayama T, Aoi N, Sato M, Haketa A . Human uncoupling protein 2 and 3 genes are associated with obesity in Japanese. Endocrine. 2008; 34(1-3):87-95. DOI: 10.1007/s12020-008-9111-9. View

14.

Dalgaard L, Sorensen T, Andersen T, Hansen T, Pedersen O . An untranslated insertion variant in the uncoupling protein 2 gene is not related to body mass index and changes in body weight during a 26-year follow-up in Danish Caucasian men. Diabetologia. 2000; 42(12):1413-6. DOI: 10.1007/s001250051312. View

15.

Kring S, Larsen L, Holst C, Toubro S, Hansen T, Astrup A . Genotype-phenotype associations in obesity dependent on definition of the obesity phenotype. Obes Facts. 2010; 1(3):138-45. PMC: 6452144. DOI: 10.1159/000137665. View

16.

Dalgaard L, Pedersen O . Uncoupling proteins: functional characteristics and role in the pathogenesis of obesity and Type II diabetes. Diabetologia. 2001; 44(8):946-65. DOI: 10.1007/s001250100596. View

17.

Klannemark M, Orho M, Groop L . No relationship between identified variants in the uncoupling protein 2 gene and energy expenditure. Eur J Endocrinol. 1998; 139(2):217-23. DOI: 10.1530/eje.0.1390217. View

18.

Oktavianthi S, Trimarsanto H, Febinia C, Suastika K, Saraswati M, Dwipayana P . Uncoupling protein 2 gene polymorphisms are associated with obesity. Cardiovasc Diabetol. 2012; 11:41. PMC: 3412711. DOI: 10.1186/1475-2840-11-41. View

19.

Maestrini S, Podesta F, Di Blasio A, Savia G, Brunani A, Tagliaferri A . Lack of association between UCP2 gene polymorphisms and obesity phenotype in Italian Caucasians. J Endocrinol Invest. 2004; 26(10):985-90. DOI: 10.1007/BF03348196. View

20.

Mottagui-Tabar S, Hoffstedt J, Brookes A, Jiao H, Arner P, Dahlman I . Association of ADRB1 and UCP3 gene polymorphisms with insulin sensitivity but not obesity. Horm Res. 2007; 69(1):31-6. DOI: 10.1159/000111793. View