探討B2-腎上腺素受體 (ADRB2) 及非偶合蛋白2  (UCP2) 基因多形性與環境因子間之交互作用對肥胖症之關係

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題名:	探討B2-腎上腺素受體 (ADRB2) 及非偶合蛋白2 (UCP2) 基因多形性與環境因子間之交互作用對肥胖症之關係
作者:	董冠言;Kuan-Yen Tung
貢獻者:	中國醫藥大學：環境醫學研究所碩士班
關鍵詞:	肥胖;原住民;B2-腎上腺素受體;非偶合蛋白2;交互作用;基因多形性;obesity;aborigine;ADRB2;UCP2;interaction;polymorphism
日期:	2009-07-08
上傳時間:	2009-08-11 16:56:28 (UTC+8)
摘要:	近年來肥胖症在許多開發中及已開發國家的盛行率都有不斷上升的趨勢。肥胖所引起常見的疾病，包括心血管疾病、高膽固醇血症、糖尿病、睡眠呼吸異常、代謝症候群等，是公共衛生重要的議題之一。肥胖的原因主要是能量代謝的失衡與脂質調控的異常所致。因為人類脂肪細胞中的B2-腎上腺素受體 (beta-2 adrenoreceptors, ADRB2) 與非偶合蛋白2 (Uncoupling proteins-2, UCP2) 分別是脂質調控與能量代謝與的候選基因，所以我們的研究目的在於探討??2-腎上腺素受體 (ADRB2：Arg16Gly) 與非偶合蛋白2 (UCP2：45-bp ins/del, -866G/A) 基因上的變異位置與肥胖症之關係。本研究設計採橫斷式研究法，研究對象為南投縣信義鄉及台中市中西區兩地接受全民健保險之成人健檢民眾共779人 (男性304人，女性475人)。將研究對象分成肥胖組261人 (BMI ?d 27；30.5 ± 3.2 kg/m2)，非肥胖組518人 (BMI < 27；23.3 ± 2.3 kg/m2)。所有研究對象簽署同意書後採集禁食血液樣本測定一般生化值，萃取DNA進行基因型鑑定，並利用問卷訪視以收集人口學資料、疾病史、生活習慣 (如抽菸、喝酒)。利用SAS統計軟體 (ver 9.1) 以適合度檢定進行各基因的對偶基因頻率與基因型是否符合哈溫平衡；以t檢定與單變項分析分別比較年齡、身體質量指數、生理生化指標在肥胖與非肥胖兩組之間及各基因型間的差異情形；以迴歸分析探討調整肥胖的危險因子後，各基因型得到肥胖的勝算比。結果顯示肥胖組較非肥胖組具有顯著較低的年齡 (58.7 歲vs. 62.1歲; P < 0.0001)；原住民較非原住民有較高的肥胖盛行率 (59.4% vs. 19.4%; P < 0.0001)。；居住在信義鄉的研究對象較居住在台中市西區者亦有較高的肥胖盛行率 (45.0% vs. 17.4%; P < 0.0001)。就原住民而言，調整干擾因子後帶有UCP2 ins/del及ins/ins基因型者較帶有del/del基因型者有較高的肥胖危險 (OR = 2.2; 95% CI = 1.03-4.60)；進一步地分析環境因子與基因對於肥胖的交互作用，經調整干擾因子後發現無運動習慣者且帶有UCP2 ins/del及ins/ins基因型者較帶有del/del基因型者得到肥胖的危險為2.3倍 (OR = 2.4; 95% CI = 1.17-5.08)；信義鄉有飲酒習慣者ADRB2帶Arg/Gly或Gly/Gly基因型者較有飲酒習慣且帶 Arg/Arg基因型者有較高的肥胖危險 (OR = 2.0; 95% CI = 1.11-3.57)。結論指出UCP2 (45-bp ins/del) 基因變異可能增加原住民肥胖的危險，且UCP2及ADRB2基因變異與環境因子間的交互作用亦會導致肥胖危險的增加；本研究結果可提供影響肥胖症的預防與治療上之參考。 The prevalence of obesity is increasing in both developing and developed countries in recent years. Obesity is a critical public health issue associated with many disorders such as cardiovascular disease, hypercholesterodemia, diabetes, obstructive sleep apnea, and metabolic syndrome. Beta-2 adrenoreceptors (ADRB2) and uncoupling proteins-2 (UCP2) gene are obesity-associated candidate genes for energy homeostasis and lipids metabolism in adipocytes, respectively. The purposes of this study were designed to investigate the interactions among the variants of ADRB2 (Arg16Gly) and UCP2 (45-bp ins/del, -866G/A) and obesity. A cross-sectional study recruited 779 subjects (man = 304, woman = 475) from Hsin-I township of Nantou County and the central-western district of Taichung City for the National Adult Health Examination Project during 2007 to 2008. Subjects were classified into 261 obese (BMI ≥ 27; 30.5 ± 3.2) cases and 518 non-obese (BMI < 27; 23.3 ± 2.3) controls. Informed consents were obtained from all subjects who provided the fasting blood samples for biochemistry measurements and DNA extraction for genotyping. The questionnaire was administrated by interview for demographic characteristics, medical history and lifestyle habits, such as smoking and alcohol consumption. All statistical analyses were performed with SAS software (Ver 9.1). The Hardy-Weinberg equilibrium for genotypic and allelic frequencies distributions were calculated by the goodness-of-fit. Chi-square tests were used to compare the genotype frequencies between the two study groups. Student''s t-test was applied to test the differences in age, BMI, lipid profile and genotypes between the two groups. Logistic regression models were carried out to estimate the odds ratios for obesity that could be explained by the variants effects of UCP2 or ADRB2 or environmental factors or interactions after adjusting other covariates. The mean age was higher in the obese group than in the non-obese group (58.7 vs. 62.1; P < 0.0001). The prevalence of obesity was significantly higher in aboriginal subjects than non-aboriginal (59.4% vs. 19.4%; P < 0.0001). The subjects who lived in the Hsin-I township of Nantou County had higher prevalence of obesity than that in the central-western district of Taichung City (45.0% vs. 17.4%; P < 0.0001). After adjusting confounding factors, the odds ratio for obesity in aboriginal subjects who carried ins/del and ins/ins genotypes of the UCP2 was 2.4 (95% CI: 1.17-5.08) those who carried del/del genotype. The subjects who used alcohol and carried ADRB2 Arg/Gly and Gly/Gly genotypes also had higher risk for obesity than those carried Arg/Arg genotype (OR = 2.0; 95% CI = 1.11-3.57). In conclusion, our study shows that the ins/del and ins/ins genotypes of UCP2 is associated with obesity aboriginal people in Taiwan. The interactions between ADRB2, UCP2 genetic variants and environmental factors may contriobute to obesity as well. These findings could provide a potential prevention or therapeutic strategies in the future.
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