| 摘要: | 研究目的：載脂蛋白E (Apolipoprotein E ，APOE )是一種多功能蛋白質，在血脂代謝和脂肪運輸上扮演一個重要的角色，研究顯示載脂蛋白E基因型與心血管疾病(Cardiovascular disease)有關。心血管疾病是一種慢性發炎所導致的疾病，主要由環境危險因子和多種遺傳基因相互調節所造成的。而這些相關於心血管疾病之危險因子，包括年紀、男性、抽菸、家族史、肥胖、糖尿病、高血壓及高血脂…等；其中膽固醇是最常做為心血管疾病風險之篩檢，特別是低密度脂蛋白膽固醇(LDL-C)的部分。本篇研究的目的是在探討台灣人載脂蛋白E基因連鎖群基因(包括TOMM40, APOE, APOCI 基因)多形性和發炎因子以及血脂間的關係性。
研究方法：本研究使用595位來自2004年台北長庚紀念醫院健康檢查中心的台灣民眾去連結之檢體做為分析樣本，其中包含了312位男性和283位女性受試者，我們實驗之基因多形性鑑定是採用聚合酶連鎖反應限制酶片段長度多型性(Polymerase Chain Reaction- Restriction fragment length polymorphism，PCR-RFLP)和TaqMan SNP Genotyping Assays得到載脂蛋白E基因型的結果(SNP genotyping data)，接著利用SPSS統計軟體來分析其基因定型與血脂和發炎標記間的關係。
結果：結果顯示在排除性別、年齡、身體肥胖質量指數、抽菸、服用降血脂藥、降血壓藥、降血糖藥後，在顯性的模式(domaint model)中，發現rs2075650之次要基因(minor allele)帶有較高的三酸甘油酯(triglyceride: TG)及較低的C反應蛋白(CRP); rs769449之次要基因帶有較高的總膽固醇(Total cholesterol)和三酸甘油酯及較低的C反應蛋白; rs429358之次要基因帶有較高的低密度脂蛋白膽固醇(LDL-C)及較低的高密度脂蛋白膽固醇(HDL-C)和C反應蛋白; rs7412之次要基因帶有較低的總膽固醇和低密度脂蛋白膽固醇; rs4420638之次要基因帶有較高的總膽固醇和三酸甘油酯及較低的C反應蛋白。另在載脂蛋白E基因ε的基因型中，我們發現ε4的人血中具有較高的總膽固醇、低密度脂蛋白膽固醇、三酸甘油酯及較低的C反應蛋白;反之帶有ε2的人的血中則較高的高密度脂蛋白膽固醇。而在交互作用的分析中，我們亦發現肥胖在ε4基因型與高密度脂蛋白膽固醇間有交互作用;另外肥胖在ε4基因型與C反應蛋白間亦有交互作用的存在。
結論: 載脂蛋白E連鎖群基因多形性與血脂及C反應蛋白間有連結關係，此外，我們亦發現肥胖在ε-基因組單倍體與高密度脂蛋白膽固醇和C反應蛋白間有交互作用。這些發現未來將可以應用於預測動脈粥狀硬化疾病。
OBJECTIVES:Apolipoprotein E (apoE, protein; APOE, gene) plays a major role in lipoprotein metabolism and lipid transport. Many investigators have described associations between apoE genotypes and coronary artery disease (CAD). Cardiovascular disease is a chronic inflammation disease caused mainly interaction by multiple genetic variable and environmental risk factors. Cardiovascular disease risk factors include age, male, smoking, family history, obesity, diabetes, hypertension and high cholesterol. The most commonly risk factor for cardiovascular diseases is low-density lipoprotein cholesterol (LDL-C). The objective of this study was to investigate the association of genetic variables of apolipoprotein cluster (including TOMM40, APOE, APOCI genes) polymorphisms between inflammation factors and blood lipids in Taiwanese.
SUBJECTS AND METHODS: A total of 595 Han Chinese subjects (including 312 men, 283 women) from Chang Gung Memorial Hosptal. The genotyping data were determined by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) and TaqMan SNP Genotyping Assays, and then used SPSS statistical software to analyze the association of genetic variance and blood lipids and inflammation markers.
RESULTS:The subjects adjusted age, sex, BMI, Current smoking, antihypertensive medication, anti diabetic treatment, and lipid lowering drug, in domaint model, the minor allele carrier of rs2075650 has higher triglyceride level and lower CRP level; rs769449 has higher total cholesterol and triglyceride level, and lower CRP level; rs429358 has higher LDL-C level, lower HDL-C and CRP level; rs7412 has lower total cholesterol and LDL-C level; rs4420638 has higher total cholesterol and triglyceride level and lower CRP level. In APOE ε-genotype, the ε4 carriers have a significant higher total cholesterol, LDL-C, triglyceride level and lower CRP level then non-carriers; whereas the ε2 with higher HDL-C level. Interaction analysis revealed interaction of obesity with ε4 genotype associated with high HDL-C level, and low CRP level.
CONCLUSION:APOE gene cluster polymorphisms are independently associated with blood lipids, and CRP level in Taiwanese. Further, ε-haplotypes interact with obesity to set HDL-C level, and CRP level. These findings have implications for the prediction of atherosclerotic disease. |
