因子VII基因多态性与冠心病患者心肌梗死风险

Polymorphisms in the factor VII gene and the risk of myocardial infarction in patients with coronary artery disease.

作者信息

Girelli D, Russo C, Ferraresi P, Olivieri O, Pinotti M, Friso S, Manzato F, Mazzucco A, Bernardi F, Corrocher R

机构信息

Department of Clinical and Experimental Medicine, University of Verona, Italy.

出版信息

N Engl J Med. 2000 Sep 14;343(11):774-80. doi: 10.1056/NEJM200009143431104.

DOI:10.1056/NEJM200009143431104

PMID:10984565

Abstract

BACKGROUND

High plasma levels of coagulation factor VII have been suggested to be predictors of death due to coronary artery disease. Since polymorphisms in the factor VII gene contribute to variations in factor VII levels, such polymorphisms may be associated with the risk of myocardial infarction, which is precipitated by thrombosis.

METHODS

We studied a total of 444 patients, 311 of whom had severe, angiographically documented coronary atherosclerosis. Of these 311 patients, 175 had documentation of a previous myocardial infarction. As a control group, 133 patients with normal coronary arteriograms were also included. We measured the levels of activated factor VII and assessed three polymorphisms in the factor VII gene, one involving the promoter (A1 and A2 alleles), one involving the catalytic region (R353Q), and one involving intron 7.

RESULTS

Each of the polymorphisms influenced factor VII levels. Patients with the A2A2 and QQ genotypes had the lowest levels of activated factor VII (66 percent and 72 percent lower, respectively, than the levels in patients with the wild-type genotypes). The frequencies of the various genotypes in the patients free of coronary artery disease were similar to those in the entire population of patients with coronary artery disease. In the latter group, there were significantly more heterozygotes and homozygotes for the A2 and Q alleles among those who had not had a myocardial infarction than among those who had had an infarction (P=0.008 for the presence of the promoter polymorphism and P=0.01 for the presence of the R353Q polymorphism by chi-square analysis). The adjusted odds ratio for myocardial infarction among the patients with the A1A2 or RQ genotype was 0.47 (95 percent confidence interval, 0.27 to 0.81).

CONCLUSIONS

Our findings suggest that certain factor VII genotypes have a role in protection against myocardial infarction. This may explain why some patients do not have myocardial infarction despite the presence of severe coronary atherosclerosis.

摘要

背景

血浆凝血因子VII水平升高被认为是冠状动脉疾病所致死亡的预测指标。由于凝血因子VII基因的多态性会导致因子VII水平的变化，因此这种多态性可能与由血栓形成引发的心肌梗死风险相关。

方法

我们共研究了444例患者，其中311例有严重的、血管造影证实的冠状动脉粥样硬化。在这311例患者中，175例有既往心肌梗死记录。作为对照组，还纳入了133例冠状动脉造影正常的患者。我们测量了活化因子VII水平，并评估了凝血因子VII基因中的三种多态性，一种涉及启动子（A1和A2等位基因），一种涉及催化区域（R353Q），一种涉及内含子7。

结果

每种多态性均影响因子VII水平。A2A2和QQ基因型的患者活化因子VII水平最低（分别比野生型基因型患者的水平低66%和72%）。无冠状动脉疾病患者中各种基因型的频率与整个冠状动脉疾病患者群体中的频率相似。在后者中，未发生心肌梗死的患者中A2和Q等位基因的杂合子和纯合子明显多于发生过心肌梗死的患者（经卡方分析，启动子多态性存在时P = 0.008，R353Q多态性存在时P = 0.01）。A1A2或RQ基因型患者发生心肌梗死的校正比值比为0.47（95%置信区间，0.27至0.81）。