在臺灣族群第9對染色體的基因多型性與冠狀動脈血管攝影的粥狀硬化程度的關係

Association between Single Nucleotide Polymorphism of Chromosome 9 with the Angiographic Severity of Coronary Atherosclerosis in the Taiwanese Population

朱俊源(Chun-Yuan Chu)

指導教授 ： 許勝雄

高雄醫學大學/醫學院/醫學研究所/臨床醫學組/碩士(2014年)

https://doi.org/10.6832/KMU.2014.00133

摘要

背景
冠狀動脈疾病(冠心病)是已開發國家導致死亡和失能的主要原因，而動脈粥狀硬化是冠心病的主要病理機轉，同時受到許多環境和遺傳因數的交互影響。當冠狀動脈粥狀硬化持續進行就會形成粥狀斑塊造成管腔狹窄，運動時可能會出現心絞痛症狀，若斑塊破裂會產生急性血栓進而造成急性冠心症，未適當治療則死亡率甚高。在冠心病的早期防治方面，除了積極控制傳統心血管危險因子如高血壓、糖尿病、高血脂以及抽煙外，使用全基因組關聯研究(GWAS)來發現相關的易感受基因已成為趨勢。第9對染色體(Chromosome 9)的單核苷酸多型性(SNP)在過去的研究已被證實與心肌梗塞的風險以及頸動脈的動脈粥狀硬化有關，然而在臺灣族群第9對染色體的基因多型性，包括9p21的rs1333049, rs4977574和rs10757278以及9q22的rs1800975，與冠狀動脈血管攝影的粥狀硬化程度的關係所知有限，故我們安排研究予以探討臺灣族群第9對染色體的基因多型性與冠狀動脈血管攝影的粥狀硬化程度的關係。

方法
自2002年2月到2008年12月，於高雄醫學大學附設醫院接受常規心導管檢查的連續病人共710位進入本研究。顯著冠心病的定義是冠狀動脈血管攝影顯示血管內徑狹窄大於50%。我們使用臨床血管分數(CVS, 0~3條血管)以及“diffuseness score”(DS, 0-11.5)並據此判定冠狀動脈粥狀硬化的嚴重程度。血液檢體則於同次心導管檢查過程中收集以備後續基因分析，單核苷酸多型性基因分析則使用 Taqman 技術。

結果
在710位參與研究的病人中，無顯著冠心病的有 162位(22.8 %)，有一條冠狀動脈疾病的有168位(23.7%)，有兩條冠狀動脈疾病的有156位(22.0%)，有三條冠狀動脈疾病的有 224 位(31.5%)。具顯著冠心病者，在rs1333049有C對偶基因以及在rs1800975有T對偶基因的頻率較 高[勝算比(OR)分別是1.31, 95% CI 1.02-1.68, p = 0.033及OR 1.33, 95% CI 1.03-1.72 , p = 0.028]。發生顯著冠心病的風險在rs1333049的CC比起GG基因型高1.73倍 (95% CI 1.04-2.87, p = 0.032)，在rs1800975的TT比起CC基因型高1.76倍 (95% CI 1.05-2.93, p = 0.030)。使用二項式對數迴歸分析校正後發現，具顯著冠心病者只有rs1333049仍然是顯著相關(p = 0.015)。單體型(haplotype)分析發現，顯著冠心病者與rs4977574、rs1333049及rs10757278呈現GCG者有顯著相關(p = 0.037)。使用單變項以及多變項迴歸分析後發現，rs1800975與CVS都是顯著相關(分別是p = 0.031以及p = 0.037)。這4個SNP與DS在多變項分析並沒有呈現相關。

結論
染色體9p21基因多型性(rs1333049)以及9q22基因多型性(rs1800975)在臺灣族群與冠狀動脈血管攝影的粥狀硬化程度有關。

關鍵字

第九對染色體 ； 9p21 ； 9q22 ； 基因多型性 ； 冠心病 ； 冠狀動脈疾病 ； 基因 ； 動脈粥狀硬化

並列摘要

Background: Coronary artery disease (CAD) is the leading cause of death and disabilities in industrially developed countries. Single nucleotide polymorphism (SNP) of chromosome 9 is associated with the risk of myocardial infarction and carotid atherosclerosis. However, little is known about the association between SNPs of chromosome 9 including rs1333049, rs4977574, rs10757278 and rs1800975 with the angiographic severity of coronary atherosclerosis in the Taiwanese population.
Methods: 710 consecutive patients scheduled for diagnostic coronary angiography were enrolled. The significant CAD was defined as diameter stenosis ?d 50%. We used clinical vessel score (CVS, 0-3 vessels) and diffuseness score (DS, 0-11.5) to evaluate the angiographic severity of coronary atherosclerosis. The TaqMan genotyping assay was used for SNPs genotyping.
Results：Among 710 enrolled patients, 162 (22.8%) were non-significant CAD, 168 (23.7%) were one-vessel disease, 156 (22.0%) were two-vessel disease, and 224 (31.5%) were three-vessel disease. The frequency of C allele of rs1333049 and T allele of rs1800975 were higher in those with significant CAD [odds ratio (OR) 1.31, 95% CI 1.02-1.68, p = 0.033 and OR 1.33, 95% CI 1.03-1.72, p = 0.028 respectively]. For the rs1333049, the OR of significant CAD for CC to GG genotype was 1.73 (95% CI 1.04-2.87, p = 0.032). For the rs1800975, the OR of significant CAD for TT to CC genotype was1.76 (95% CI 1.05-2.93, p = 0.030). Binary logistic regression analysis found only rs1333049 was still associated with the presence of significant CAD (p = 0.015). Haplotype analysis found GCG of rs4977574, rs1333049 and rs10757278 was associated with the presence of significant CAD (p = 0.037).Univariate and multivariate regression analysis found significant associations between CVS and rs1800975 (p = 0.031 and 0.037, respectively).None of 4 SNPs was associated with DS after multivariate analysis.
Conclusion：The SNP rs1333049 on chromosome 9p21 and rs1800975 on chromosome 9q22 were associated with the angiographic severity of coronary atherosclerosis in the Taiwanese population.

並列關鍵字

Chromosome 9p21 ； Chromosome 9q22 ； Polymorphism ； Coronary artery disease ； Gene ； Atherosclrosis

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