與血管再狹隘相關基因多型性的後設分析

The meta-analysis of the gene polymorphism related with coronary artery restenosis.

林冠宇(lin kuan yü)

指導教授 ： 吳家樂

亞洲大學/資訊學院/生物資訊學系碩士班/碩士(2007年)

摘要

目前許多研究顯示，發生冠狀動脈再狹隘（Restenosis）的個案，與遺傳有所相關性。而這些相關性的基因，主要是因序列上產生細小的變化，因而改變蛋白的結構或者轉錄機制，進而控制血管在進行一些細胞活動時的變化，而這些差異就是來自基因的單核苷酸多變性（Single Nucleotide Polymorphism, SNP）。單一基因上的一種多型性，並不代表這變化完全的改變了這個基因的功能，有時這些基因變化是具有多種 SNP 的連鎖性相關，所以利用統計的方法，找出哪些基因對於再狹隘的性狀控制具有連鎖性的影響，會是有效率的診斷方針。
與再狹隘有相關性的基因，目前已知可能有七種，而這七種之中，腎素-血管收縮素轉化酶系統中的血管收縮素轉化酶，及內皮細胞一氧化氮合成酶，對於冠狀動脈疾病在遺傳上的表現，最常被研究。在此篇研究中，我們透過文獻探討找出與血管收縮素轉化酶、血管收縮素原、第一型血管收縮素受器以及內皮細胞一氧化氮合成酶的相關對偶基因型數據，進行後設分析，分析這四個基因與冠狀動脈再狹隘的相關性。
本研究在這兩個基因中，從後設分析得知ACE的D型對偶基因、AGT的T對偶基因、以及eNOS -786C對偶基因對於冠狀動脈的再狹隘具有相關性，且可由血漿中的ACE的含量以及硝酸鹽/亞硝酸鹽的濃度，配合AGT的T對偶基因的檢測，來預測再狹隘疾病的發生可能性。
由我們的研究結果，我們建議meta-analysis必須首先用於這一類的研究，以評估研究的合理性。

關鍵字

與血管

並列摘要

A lot of researches have shown that the cases of coronary artery restenosis are related with heredity. Mutations in the restenosis related genes maybe result in protein conformational change or decrease in protein activity. The changed fragment may be a single nucleotide or more, and its locus may be located at exon or intron. These differences are called single nucleotide polymorphism （SNP）. But these change do not exist alone, they coexist with two or more SNPs, and it may be linkage. It is reported that at least seven genes are highly relevant to restenosis, for instance, angiotensin-converting enzyme of the renin–angiotensin system (RAS) and endothelial nitric oxide synthase are two of the highly studied genes among them.
In this research, patients’ data of angiotensin-converting enzyme, angiotensinogen , angiotensin II type I receptor, and endothelial nitric oxide synthase are collected through literature reviewing. Meta-analysis approach is applied to find out the linkage genes which influence the restenosis of coronary artery. The relative risk of these SNPs in restenosis of coronary artery is estimated. The results show that the D allele of ACE, aspatic acid of AGT 298, and C allele of eNOS -786 are related with restenosis of coronary.
We suggest that meta-analysis of the gene polymorphism related with coronary artery restenosis must be used first before the study, and this kind of approach can be used in other area of research.

並列關鍵字

artery restenosis

參考文獻

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