Wang T N, Huang M C, Lin H L, Hsiang C H, Ko A M J, Chang W T, Ko Y C
Faculty of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan.
Int J Obes (Lond). 2007 Nov;31(11):1746-52. doi: 10.1038/sj.ijo.0803648. Epub 2007 May 15.
Human uncoupling proteins 2 and 3 (UCP2 and UCP3) are two mitochondrial proteins that are involved in the control of metabolism of fatty acid and possibly protect against oxidative damage. The aim of this study was to analyze genetic associations of four polymorphisms of the UCP2 and UCP3 genes with insulin, leptin concentration and obesity in Taiwan aborigines.
Four polymorphisms were compared in 324 obese (body mass index (BMI) > or =30 kg/m(2)) and overweight (30>BMI > or =25 kg/m(2)) subjects, and 114 normal weight subjects (BMI <25 kg/m(2)) in an aboriginal community of southern Taiwan. Anthropometric characteristics and fasting levels of insulin, leptin, triglycerides and cholesterol were measured.
Before and after adjusting for age distribution, only the Val55 allele in exon 4 of the UCP2 gene increased the risk of overweight and obesity (adjusted odds ratio (OR)=2.02, P=0.004) in comparison with Ala55. UCP2 V55V is also associated with higher fasting insulin levels than A55V (P=0.01) and A55A (P=0.04) in the obese/overweight group. Using the COCAPHASE program of the UNPHASED software, haplotype analysis of three single nucleotide polymorphisms (A55V-G866A-C-55T) revealed that A-G-C (73% in obese subjects and 77% in controls) was the most common haplotype and that the haplotype V-A-T (13% in obese subjects and 5% in controls) was significantly increased in obese and overweight subjects (BMI > or =25 kg/m(2)) (OR=2.62, P<0.001).
UCP2 A55V variant might predispose to obesity and Val55 allele to confer population-attributable risk for 9.5% of obese disorders and increase insulin concentrations. The V-A-T haplotype within UCP2-UCP3 gene cluster is also significantly associated with obesity in Paiwan aborigines.
人类解偶联蛋白2和3（UCP2和UCP3）是两种线粒体蛋白，参与脂肪酸代谢的调控，并可能预防氧化损伤。本研究旨在分析台湾原住民中UCP2和UCP3基因的四种多态性与胰岛素、瘦素浓度及肥胖的遗传关联。
在台湾南部一个原住民社区中，对324名肥胖（体重指数（BMI）≥30 kg/m²）和超重（30＞BMI≥25 kg/m²）受试者以及114名正常体重受试者（BMI＜25 kg/m²）的四种多态性进行了比较。测量了人体测量学特征以及胰岛素、瘦素、甘油三酯和胆固醇的空腹水平。
在调整年龄分布前后，与Ala55相比，UCP2基因第4外显子中的Val55等位基因增加了超重和肥胖的风险（调整后的优势比（OR）=2.02，P=0.004）。在肥胖/超重组中，UCP2 V55V与空腹胰岛素水平高于A55V（P=0.01）和A55A（P=0.04）也相关。使用UNPHASED软件的COCAPHASE程序，对三个单核苷酸多态性（A55V-G866A-C-55T）进行单倍型分析，结果显示A-G-C（肥胖受试者中占73%，对照组中占77%）是最常见的单倍型，而单倍型V-A-T（肥胖受试者中占13%，对照组中占5%）在肥胖和超重受试者（BMI≥25 kg/m²）中显著增加（OR=2.62，P＜0.001）。
UCP2 A55V变异可能易导致肥胖，Val55等位基因导致9.5%的肥胖症具有人群归因风险，并增加胰岛素浓度。UCP2-UCP3基因簇内的V-A-T单倍型在排湾族原住民中也与肥胖显著相关。
