細胞附著因子的基因多型性和冠動脈疾病的相關性探討

Relationship of Genetic Polymorphisms of Intercellular Adhesion Molecule-1 with Coronary Artery Disease in Taiwan

周祈宏(Chiu-Hung Chou)

指導教授 ： 王博輝

中山醫學大學/醫學院/醫學研究所/博士(2016年)

摘要

冠狀動脈疾病(coronary artery disease; CAD)的發病機理主要是冠狀動脈粥樣硬化，引起在冠狀動脈的血管壁的慢性發炎反應。細胞間粘附分子-1(intercellular adhesion molecule-1; ICAM-1）在發炎反應和動脈粥樣硬化的發展中扮演了重要角色。很少有台灣ICAM-1基因多型性與CAD的關聯性研究報告。因此，我們進行了一項ICAM-1的單核苷酸多態性(single nucleotide polymorphism; SNP)研究，關於rs5491 (K56M)，rs5498 (A1548G)，rs281432 (C8823G)和rs3093030 (C-286T)的SNP與CAD的關聯性。
本實驗共收集525位男性和女性受試者，在台灣中山醫學大學附設醫院接受選擇性冠狀動脈造影，並接受即時聚合酶鏈反應 (real time polymerase chain reaction; real time PCR)和基因定序(genotyping)的方法進行ICAM-1的SNP基因組分型。並對ICAM-1的SNPs，單倍體(haplotypes)，流行病學，臨床特徵及CAD的關係與否進行了分析。 SNPs包括了rs5498 (A1548G in exon 6)，rs5491(K56M，in exon 2)，rs281432 (C8823G in intron 2)和rs3093030 (C-286T)。
結果發現，rs281432（C8823G）是唯一ICAM-1的SNP影響的會CAD的發生。多變量分析顯示 ICAM-1 SNP rs281432 CC/CG [p=0.016; odds ratio (OR): 2.56, 95% confidence interval (CI): 1.19-5.56], 男性 (p=0.018; OR: 1.66, 95% CI: 1.09-2.51), 過去七天使用aspirin (p=0.001; OR: 2.05, 95% CI: 1.33-3.14), 高血壓 (p<0.001; OR: 2.15, 95% CI: 1.42-3.25), 血液 cardiac troponin I 升高 (p<0.001; OR: 2.14, 95% CI: 1.47-3.24) 和最近24 hours發生嚴重心絞痛 (p=0.001; OR: 1.97, 95% CI: 1.31- 2.95) 會增加CAD的風險。我們發現，ICAM-1的SNP rs281432是一個可用來預測的CAD發生的獨立因子。 ICAM-1 SNP rs281432同型合子突變GG可以降低台灣人在CAD的易感性 (susceptibility)。

關鍵字

冠狀動脈疾病 ； 基因多型性 ； 單倍型 ； 細胞間粘附分子-1 ； rs281432 ； 台灣人

並列摘要

The main pathogenesis of coronary artery disease (CAD) is coronary artery atherosclerosis, a chronic inflammatory disease in the vessel walls of the coronary artery. Intercellular adhesion molecule-1 (ICAM-1) displays an important role in the development of the inflammatory reaction and atherosclerosis. Few studies report the association of ICAM-1 genetic polymorphisms with CAD in Taiwanese subjects. Therefore, we conducted a study to associate the single nucleotide polymorphisms (SNPs) of ICAM-1, rs5491 (K56M)，rs5498 (A1548G)，rs281432 (C8823G) and rs3093030 (C-286T) with CAD. Five hundred and twenty-five male and female subjects, who received elective coronary angiography under medical indication in Chung Shan Medical University Hospital, Taichung, Taiwan were recruited to determine four ICAM-1 SNPs by using real time-polymerase chain reaction and genotyping. The relationships among ICAM-1 SNPs, haplotypes, demographic characteristics, clinical variables and CAD were analyzed. This study showed that rs281432 (C8823G) is the only ICAM-1 SNP which affects the development of CAD. Multivariate analysis revealed that ICAM-1 SNP rs281432 CC/CG [p=0.016; odds ratio (OR): 2.56, 95% confidence interval (CI): 1.19-5.56], male gender (p=0.018; OR: 1.66, 95% CI: 1.09-2.51), aspirin use in the past 7 days (p=0.001; OR: 2.05, 95% CI: 1.33-3.14), hypertension (p<0.001; OR: 2.15, 95% CI: 1.42-3.25), serum cardiac troponin I elevation (p<0.001; OR: 2.14, 95% CI: 1.47-3.24) and severe angina in recent 24 hours (p=0.001; OR: 1.97, 95% CI: 1.31- 2.95) increase the risk of CAD. In conclusion, ICAM-1 SNP rs281432 is an independent factor to predict the development of CAD. ICAM-1 SNP rs281432 homozygotic mutant GG can reduce the susceptibility to the CAD in Taiwanese subjects.

並列關鍵字

Coronary artery disease ； genetic polymorphism ； haplotype ； intercellular adhesion molecule-1 ； rs281432 ； Taiwanese

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