Ghrelin 基因多形性與腦梗塞及其危險因子之相關性研究

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題名:	Ghrelin 基因多形性與腦梗塞及其危險因子之相關性研究 The Relationships of Ghrelin Gene Polymorphisms with Ischemic Stroke and Cerebrovascular Risk Factors in Taiwan
作者:	王睿 Wang, Jui
貢獻者:	白其卉
關鍵詞:	Ghrelin,Ghrelin基因多形性,腦梗塞 Ischemic stroke,cerebrovascular risk factors,Ghrelin,Ghrelin polymorphisms
日期:	2013-06-18
上傳時間:	2018-09-27 14:43:57 (UTC+8)
摘要:	研究背景：台灣地區隨著飲食西化及生活習慣影響，腦血管疾病逐漸變為常見的疾病形式，而在逐漸高齡化的社會中，如何預防腦中風的發生亦會是重要的公共衛生目標。近年來有研究指出Ghrelin可能與心血管疾病的發生有相關，Ghrelin為一個內源性配體，可以與生長激素分泌接受器結合，促使腦下垂體分泌生長激素，生長激素被認為與血管內皮損傷的修復有關。因此，本研究欲探討台灣人族群中Ghrelin基因多形性與腦梗塞及心血管危險因子之關係。材料方法：本研究是醫院為基礎之病例對照研究。研究族群為來自大台北地區，選擇新光醫療財團法人新光吳火獅紀念醫院為就醫場所之30歲以上族群。病例組為神經科病房腦梗塞個案(N=199)及神經科門診腦梗塞穩定期個案(N=67)；對照組為神經科門診無中風徵候個案(N=80)及2004年(I)跟2009年(II)士林地區健檢個案(I=433；II=127)。利用結構式問卷收集研究對象之基本人口學資料，以聚合酶連鎖反應-限制酶片段長度多形性及Tetra-primer ARMS-PCR方法進行基因判定，用酵素免疫分析法進行Ghrelin濃度測定。利用多變項邏輯斯迴歸進行Ghrelin基因型及濃度與各危險因子之多變項分析。結果：本研究未觀察到rs34911341位點變異。校正年齡、性別及收案時間後，rs26311位點中CG基因型罹患高血壓(OR=0.69, p<0.05)、高膽固醇血症(OR=1.50, p<0.05)、高三酸甘油酯血症(OR=1.44, p<0.05)、高低密度脂蛋白血症(OR=1.60, p<0.05)風險較GG基因型有差異；rs26312位點帶CT基因型者其高低密度脂蛋白血症(OR=1.38, p<0.05)風險與CC基因型有差，而rs4684678位點CT基因型其肥胖風險為2.46倍(p<0.01)。在校正傳統危險因子後，僅rs26311位點帶CG基因型者罹患腦梗塞風險(OR=0.47, p<0.05)顯著較低。rs696217位點帶有A對偶基因與高三酸甘油酯血症對於腦梗塞呈現顯著拮抗作用，而rs26312位點帶有T對偶基因則與肥胖、rs4684678中CT基因型有吸菸者對於腦梗塞有顯著加成作用。而濃度方面，Acyl Ghrelin與高膽固醇血症、高三酸甘油酯血症及代謝症候群呈現負相關(Ptrend =0.02, 0.03, 0.03)。結論： Acyl Ghrelin濃度與血脂異常及代謝症候群相關。rs26311及rs26312位點與多種血管危險因子(如高血壓及血脂異常)呈現顯著關係，而rs4684678位點則與肥胖有關，rs26311位點與腦梗塞呈現顯著相關。因此Ghrelin基因多形性也許可以作為腦血管疾病及其共病症之生物標記。 Background：The cerebrovascular disease is the leading third cause of death in Taiwan for 2 decades. The incidence and prevalence of ischemic stroke are increasing rapidly among the population over 65 years old. The burden of ischemic stroke is increasing each year. As an aging society, prevention of stroke becomes a significant health concern in Taiwan. Ghrelin is a novel endogenous ligand for the growth hormone secretagogue receptor. Recently, it has been shown that Ghrelin may play a role in the regulation of atherosclerosis and cardiovascular disease. The aim of this study is to investigate the association between Ghrelin polymorphisms and ischemic stroke as well as cerebrovascular risk factors in Taiwanese population. Materials and Methods：This study is a hospital-based case-control study. We conducted 266 ischemic stroke patients (199 first-ever cases and 67 stable cases from 1996 to 1999) and 640 controls (80 controls from 1996 to 1999, 433 controls in 2004 and 127 controls in 2009) from Shin Kong Wu Ho-Su Memorial Hospital. All cases and controls were interviewed by well-trained interviews using standardized structured questionnaires. Genetic polymorphisms were evaluated by PCR-RFLP and Tetra-primer ARMS-PCR. Ghrelin concentrations were evaluated by ELISA. Using logistic regression to investigate the relationships among Ghrelin polymorphisms, Ghrelin concentrations and ischemic stroke, in merging cerebrovascular risk factors. Results：Ischemic stroke patients had higher waist-to-hip Ratio, levels of uric acid, triglyceride, glucose and lower HDL-cholesterol level compared with controls. No rs34911341 variants were found in our study subjects. After adjusted age, gender & research time, the subjects who with C-1062G genotype had significant 0.69-folds risk of hypertension, 1.50-folds risk of hypercholesterolemia, 1.44-folds risk of hypertriglyceridemia, 1.60-folds risk of hyper-LDL cholesterolemia and 2.08-folds risk of plaque compared with G-1062G genotype. Subjects with C-994T genotype, we observed a statistically significant increased risk of hyper-LDL cholesterolemia (adjusted OR=1.38, p<0.05) and plaque(adjusted OR=2.17, p<0.05) compared with C-994C genotype. Subjects with C-887T genotype had higher obesity risk(adjusted OR=2.46, p<0.01) compared with C-887C genotype. After adjusted various cerebrovascular risk factors, only C-1062G had lower risk of ischemic stroke (adjusted OR=0.47, p<0.05) compared with G-1062G genotype. The joint effect between gene and risk factors were also examined. The results showed that 72Met and hypertriglyceridemia was antagonistic for ischemic stroke, -994T and obesity, -887T and smoking were synergistic for ischemic stroke. Acyl Ghrelin levels were inversely correlated with hypercholesterolemia, hypertriglyceridemia and metabolic syndrome (Ptrend =0.02, 0.03, 0.03). Conclusion：In summary, rs26311and rs26312 SNPs were associationed with cerebrovascular risk factors especially various lipid profiles. rs4684678 SNP was associationed with obesity. rs26311 SNP alse significant associationed with ischemic stroke in Taiwanese population. Therefore, Ghrelin polymorphisms may have some roles in the etiology of ischemic stroke.
描述:	碩士論文指導教授-白其卉共同指導教授-陳焜林委員-邱弘毅委員-連立明委員-謝芳宜
資料類型:	thesis
顯示於類別:	[公共衛生學系暨研究所] 碩博論文

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