| 摘要: | 背景：本研究利用病例對照研究法探討代謝症候群與三磷酸腺苷結合盒轉運子1 (ATP-binding cassette transporter 1,ABCA1)基因多型性(G1051A、G2706A及A3044G)、環境及脂質代謝相關因子之關聯性。
材料與方法：研究對象為2007年參與南投縣信義鄉及台中市中西區之成人健檢者。其中代謝症候群個案272名，並以無代謝症候群之民眾作為對照組(395名)，原住民族群佔35%，非原住民佔65%。收集問卷資料及生理生化值，以聚合酶鏈鎖反應-限制片段長度基因多型性試驗(PCR-RFLP assay)進行三磷酸腺苷結合盒轉運子1基因中exon 7的G1051A、exon 16的G2706A及exon 18內的A3044G三種單核苷酸多型性(single nucleotide polymorphsim，SNP)檢測。
結果：以人口學資料分析顯示患有代謝症候群者中原住民、教育程度低、有抽菸、飲酒、吃檳榔、沒有運動習慣的比例較高。而調整性別、年齡後，原住民比非原住民有較高之三酸甘油脂濃度(209.7 vs. 188.5 mg/dl)、丙麥胺酸轉移脢濃度(100.2 vs. 42.5u/l)。另外，再調整種族的效應後，代謝症候群個案相較於對照組有顯著較高的血糖(122.2 vs. 89.5 mg/dl)、三酸甘油脂(195 vs. 97.8 mg/dl)、丙麥胺酸轉移脢濃度(69.1 vs. 34.8 mg/dl)、收縮壓(139.9 vs. 129.2 mm-Hg)、舒張壓(85.7 vs. 78.7 mm-Hg)、腰圍(91.9 vs. 80.0 cm)、BMI(28.1 vs. 24.2 kg/m2)；顯著較低的高密度膽固醇濃度(40.6 vs. 53.3 mg/dl)。此外，患有代謝症候群者相較於對照組有較高的心臟病(19.1% vs. 13.5%)、高血壓(60.1% vs. 30.0%)、肥胖症(61.7% vs. 20.8%)、高尿酸血症(25.1% vs. 8.2 %)、高血脂(25.8% vs. 15.9 %)、糖尿病(25.8% vs. 3.9%)及肝功能異常(18.0% vs. 8.2%)的比例。藉由多變量邏輯斯迴歸分析發現，有嚼檳榔習慣者罹患代謝症候群危險性是無此習慣者的2.37倍(95% CI=1.82-3.78)，有喝咖啡習慣者罹患代謝症候群危險性是無此習慣者的0.34倍(95% CI=0.15–0.76)。此外，本研究並未發現ABCA1 G1051A 、G2706A及A3044G單核苷酸多型性與代謝症候群之關聯性。原住民攜帶1051A allele者其總膽固醇濃度明顯較低、透過複回規模式則發現非原住民攜帶2706A allele者其高密度膽固醇濃度顯著高於野生型(GG)者，進一步做haplotype(單倍體)與代謝症候群相關性的分析，在控制干擾因子之後，發現haplotype ABCA1(1051A, 2706A, 3044G)會顯著增加罹患代謝症候群的危險性(OR=7.6; 95% CI=2.37–24.31)。
結論：本研究發現ABCA1基因之G1051A、G2706A及A3044G單核苷酸多型性單倍體組合形態，可以作為預測代謝症候群罹病風險的參考。
Background：The metabolic syndrome(Mets) has become an epidemic issue worldwide. Indiviauals with the Mets are at an increased risk of coronary heart disease and other diseases related to plaque buildups in artery walls (e.g., stroke and peripheral vascular disease) and type 2 diabetes, and it remains a major public health problem. In this study, we examined the association between Mets and single-nucleotide polymorphisms of ABCA1 gene and their related factors.
Methods：The study comprised 667 subjects (272 cases and 395 controls) with 35% aborigines and 65% non-aborigines who lived at Hsin-Yi area of Nantou County and Taichung County in 2007. Blood samples from our participators were collected, and analyzed for biochemical markers. The ABCA1 genotypes in exon 7 G1051A, exon 16 G2706A and exon 18 A3044G were performed by the PCR-restriction fragment length polymorphism assay. To confirm the genotyping results, selected PCR-amplified DNA samples were examined by DNA sequencing.
Results：Aborigines, received less education, and were more likely smoking, drinking, areca chewing and no exercise, and prevalent in Mets as well. Adjusting for age and gender effects, the mean triglyceride(209.7 vs. 188.5 mg/dl) and γ-GT level(100.2 vs. 42.5u/l), Mets was more prevalent in aboriginal subjects than in non-aboriginal subjects. In addition, after the adjustment for age ,gender and race , Mets paitients had higher glucose(122.2 vs. 89.5 mg/dl), triglyceride(195 vs. 97.8 mg/dl), γ-GT (69.1 vs. 34.8 mg/dl), systolic pressure(139.9 vs. 129.2 mm-Hg), diastolic pressure(85.7 vs. 78.7 mm-Hg), waist(91.9 vs. 80.0 cm), BMI(28.1 vs. 24.2 kg/m2), but lower HDL level(40.6 vs. 53.3 mg/dl). They also had higher proportions of heart disease(19.1% vs. 13.5%), hypertension(60.1% vs. 30.0%), obesity(61.7% vs. 20.8%), hyperuricemia (25.1% vs. 8.2 %), hyperlipidemia(25.8% vs. 15.9 %), diabetes(25.8% vs. 3.9%), liver complaint(18.0% vs. 8.2%) than controls. Multiple logistic regression analysis showed that areca chewing habits significantly associated with a increased risk for Mets(OR=3.46; 95% CI=1.27-9.4). Coffee drinking habits significantly associated with a decreased risk for Mets(OR=0.34; 95% CI=0.15-0.76). But, we found no significant association between cigarette smoking, alcoholic consumption and metabolic syndrome. Besides, there were no significant associations between the ABCA1 G1051A, G2706A, A3044G SNPs and Mets. The aborigine 1051A allele carriers had a lower level of total-cholesterol(compare with wild type). Through the multiple regression , we found the non-aborigine 2706A allele carriers had a higher level of HDL(compare with wild type GG). Furthermore, through the haplotype analysis, after adjusting for confounding. One haplotype containing ABCA1(1051A, 2706A, 3044G) was significantly associated with a increased risk for Mets. (OR=7.6; 95% CI=2.37–24.31)
Conclusion：This study suggested that the ABCA1 haplotype represents an important locus for predicting risk of metabolic syndrome . |
