動脈硬化之基因多型性研究 : 四型磷酸二酯酶基因、亞甲基四氫葉酸還原酶基因與動脈硬化之相關性

Genetic Polymorphisms and Atherosclerosis: Associations Between Phosphodiesterase 4D (PDE4D)、Methylene Tetrahydrofolate Reductase (MTHFR) Genes and Atherosclerosis

廖翊筑(Yi-Chu Liao)

指導教授 ： 卓夙航

高雄醫學大學/醫學院/醫學遺傳學研究所/碩士(2007年)

https://doi.org/10.6832/KMU.2007.00042

摘要

背景: 動脈硬化為心血管疾病及腦中風共同的致病機轉。過去研究發現遺傳因子可決定個體暴露於環境危險因子時，產生動脈硬化的傾向。為了探討遺傳因素對動脈硬化的影響，本論文以兩種不同的研究設計討論動脈硬化之易感性基因。
方法: 第一個子研究以疾病-對照組的相關性研究探討四型磷酸二酯酶基因(PDE4D)基因多型性與年輕型中風的關係；第二個子研究分析亞甲基四氫葉酸還原酶基因(MTHFR)基因多型性與動脈硬化中間性狀的相關性，這些中間性狀包括三種黏附分子及氮氧化物濃度，並討論MTHFR基因是否藉由調控血中高半胱氨酸濃度而影響動脈硬化。
結果: PDE4D基因上的rs702553與中國人年輕型中風有關，且其遺傳模式呈現加成性效果；帶有T對偶基因的人罹患缺血性腦中風的風險將增加為1.36倍，其效果在無高血壓的個體更為顯著。第二個研究發現帶有MTHFR 677 C>T基因多型性T對偶基因的個體，有較高的血管細胞黏附分子濃度，較高的高半胱氨酸濃度和較低的氮氧化物濃度，顯示T對偶基因為動脈硬化的危險因子。
結論: PDE4D基因與MTHFR基因上的單核苷酸基因多型性能影響動脈硬化的形成；經由尋找動脈硬化的易感性基因，我們能更深入的瞭解致病機轉。

關鍵字

動脈硬化 ； 基因多型性 ； 四型磷酸二酯酶基因 ； 亞甲基四氫葉酸還原酶基因 ； 年輕型中風

並列摘要

Background: Atherosclerosis is the common pathogenesis of coronary heart disease and stroke. The heritability of cardiovascular disease was estimated to be around 40%-60%, which indicated an important role played by genetic factors. The purpose of this dissertation was to determine the susceptibility genes of atherosclerosis.
Methods: The study was divided into two parts. The first one enrolled 190 young stroke patients and 211 healthy controls, and tested four single nucleotide polymorphisms (SNPs) at the phosphodiesterase 4D (PDE4D) gene. The second one recruited 297 healthy volunteers from the community and tested the associations between the methylene tetrahydrofolate reductase (MTHFR) genetic polymorphisms and atherosclerosis surrogate markers, including three kinds of adhesion molecules and nitric oxide.
Results: The T allele of rs702553 at the PDE4D gene was associated with ischemic stroke in young adults, and it appeared to have an additive effect. The genetic effect was confined in the normotensive participants. The second study showed that the T allele of SNP 677 C>T at the MTHFR gene was associated with higher serum level of soluble vascular cellular adhesion molecule (sVCAM), higher level of homocysteine , but lower level of nitric oxide (NOx). Our data indicated that MTHFR gene could influence the pathogenesis of atherosclerosis, at lest in part, through the dysregulation of adhesion molecules and NOx.
Conclusions: The genetic polymorphisms at the PDE4D and MTHFR genes could predispose to atherosclerosis risks in our population.

並列關鍵字

atherosclerosis ； SNPs,PDE4D gene ； MTHFR gene ； young stroke

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