台灣南部某原住民族群UCP2及UCP3單一核苷酸多型性之肥胖危險性及單套基因型分析

The obesity risk and haplotypes analysis of UCP2 and UCP3 polymorphisms in an aboriginal tribe of southern Taiwan

林秀玲(Hsiu-Ling Lin)

指導教授 ： 王姿乃

高雄醫學大學/健康科學院/公共衛生學研究所/碩士(2005年)

摘要

研究目標：探討台灣南部地區某排灣族原住民族群UCP2及UCP3單一核苷酸多型性的差別、連鎖不平衡的相關及環境因素對過重及肥胖的相關性。

研究設計：以橫斷(cross-sectional)研究方法收集台灣南部某排灣族社區70歲以下原住民族群的問卷、血液檢體及體檢資料，用於分析飲食、環境因素及UCP2基因之3’UTR I/R、Ala55Val、G-866A與UCP3基因之C-55T、V102I等單一核苷酸多型性(SNPs)對肥胖的影響。

結果：研究發現過重/肥胖組(BMI>25kg/m2)之腰圍、臀圍、腰臀圍比及血壓的平均值+標準差皆高於非肥胖組(<25kg/m2)並達統計上之顯著水準，而高血壓(P=0.008)、心臟病(P=0.047)及高血脂症(P<0.001)與過重及肥胖之間可能有相關。此外，UCP2 Ala55Val與BMI(P=0.04)、log空腹胰島素(P=0.03)及log空腹瘦素(P=0.01)皆達統計上之顯著相關，進一步將過重/肥胖組與非肥胖組分開來看，在過重/肥胖組中，也同樣發現UCP2 Ala55Val單一核苷酸多型性與log空腹胰島素(P=0.02)及log空腹瘦素(P=0.04)達統計上之顯著相關。再由散佈圖來觀察UCP2 Ala55Val單一核苷酸多型性(CC、CT、TT)與空腹血清胰島素及肥胖的相關，發現同型合子TT型之BMI的變異量有77%可由空腹血清胰島素來解釋(Rs2=0.77；P=0.002)，顯示帶有TT型的排灣族原住民有較高的BMI值可能是與空腹血清胰島素有關。
本研究中UCP2 Ala55Val與過重/肥胖有關聯性存在(P=0.01)，在控制年齡後發現UCP2 Ala55Val中CT型及TT型的過重危險對比值是CC型的1.83倍(95%C.I：1.06-3.15)(P=0.03)，肥胖危險對比值=2.54倍(95%C.I：1.40-4.59)(P=0.002)；如果單看對偶基因〝T 〞對〝C 〞的過重危險對比值為1.84倍(95%C.I：1.12-3.03)(P=0.02)，肥胖危險對比值=2.32(95%C.I：1.36-3.95)(P=0.002)。UCP2 3’UTR I/UCP2 55Val(T)及UCP2 55Val(T)/UCP2 -866A有連鎖不平衡的相關存在，UCP255Val(T)/UCP3-55T兩基因之間亦有連鎖不平衡相關存在，而UCP2 55Val(T)/UCP2-866A/UCP3-55T之危險對比值在過重組為2.56倍(P=0.003)，在肥胖組為2.70倍(P=0.002)。

結論：本研究中發現UCP2 Ala55Val與過重(BMI25-30kg/m2)及肥胖(BMI>30kg/m2)、空腹血清胰島素及空腹血清瘦素有關，其中帶有TT型的原住民有較高的BMI值可能是與空腹血清胰島素有關，並且帶有CT/TT型的過重及肥胖的危險對比值也比CC型的高，並且UCP2與UCP3兩基因的單一核苷酸多型性(variants)彼此間對過重及肥胖的危險性是有連鎖不平衡相關的。

關鍵字

單套基因型 ； 危險對比值 ； 肥胖 ； 原住民

並列摘要

Objective：The objective of the study was to examine the association and linkage disequilibrium between the risk of obesity and the SNPs of UCP2 and UCP3 and environment factors in a Paiwan aboriginal tribe of southern Taiwan.

Design：We conducted a cross-secional study, then collected the questionnaires, blood samples and the healthy informations of Paiwan aborigines under seventy years old.In order to analyze the obesity risk between food intake frequency, environmental factors and the polymorphisms of 3’UTR Ins/Rep、Ala55Val and G-866A of UCP2 and C-55T、V102I of UCP3.

Results：We found the Means±S.Ds of waist, hip, waist-to-hip ratio and blood pressure among overweight/obesity subjects(BMI>25kg/m2) were higher than non-obesity subjects and had statistical significance. Hypertension (P=0.008), heart disease (P=0.047) and hyperlipemia (P<0.001) were correlated with obesity. The UCP2 Ala55Val variants significant associated with BMI (P=0.04), loginsulin (P=0.027) and logleptin (P=0.012). BMI was classified into three groups：obesity (BMI>30kg/m2)、overweight(BMI25-30kg/m2) and non-obesity(BMI≦25kg/m2), and the UCP2 Ala55Val variants of overweight/obesity were significant associated with loginsulin (P=0.02) and logleptin (P=0.04). Then observed the scatter plot, we found subjects with homozygotes (TT) of UCP2 Ala55Val, whose BMI were positively correlated with insulin (Rs2=0.77；P=0.002). There was a significant association between obesity and variants of UCP2 Ala55Val (P=0.01). Adjusted for difference in age, we also found the obesity risk(AOR) of heterozygotes ( CT) and homozygotes (TT) of UCP2 Ala55Val to homozygotes (CC) had significant increased.The AOR of overweight was 1.83(1.06-3.15), and the AOR of obesity was 2.54(1.40-4.59). Then, observed alleles T to alleles C of UCP2 Ala55Val also had significant increased.The AOR of overweight was 1.84(1.12-3.03), and the AOR of obesity was 2.32(1.36-3.95). The UCP2 of 3’UTR I/55Val(T) and 55Val(T)/-866A were in linkage disequilibrium. The UCP2 55Val(T)/UCP3-55T were also in linkage disequilibrium.The obesity risk(OR) of UCP2 55Val(T)/UCP2-866A/UCP3-55T in overweight was 2.56(P=0.003) and in obesity was 2.70(P=0.002).

Discussion：In our study, we found the association between UCP2 Ala55Val and overweight/obesity, insulin and leptin. Paiwan aborigines of southern Taiwan who carry homozygotes TT of UCP2 Ala55Val have higher BMI and insulin. The overweight/obesity risk of heterozygotes CT and homozygotes TT was higher than homozygotes CC, and the SNPs of UCP2 and UCP3 to overweight /obesity risk were in linkage disequilibrium association.

並列關鍵字

Odds ratio (OR) ； Obesity ； Haplotype ； Aborigine

參考文獻

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