Polymorphisms in the factor VII gene and the risk of myocardial infarction in patients with coronary artery disease
Polymorphisms in the factor VII gene and the risk of myocardial infarction in patients with coronary artery disease
复制标题
DOI：
10.1056/nejm200009143431104
复制
发表时间：
2000-09-14
影响因子：
158.5
通讯作者：
Corrocher, R
中科院分区：
文献类型：
--
作者：
Girelli, D;Russo, C;Corrocher, R
背景：血浆凝血因子VII水平升高被认为是冠状动脉疾病致死的预测因素。由于因子VII基因的多态性导致因子VII水平的差异，这种多态性可能与心肌梗死的风险相关，心肌梗死是由血栓形成引发的。
方法：我们共研究了444例患者，其中311例有严重的、经血管造影证实的冠状动脉粥样硬化。在这311例患者中，175例有既往心肌梗死的记录。作为对照组，还包括133例冠状动脉造影正常的患者。我们测量了活化因子VII的水平，并评估了因子VII基因的三种多态性，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：每种多态性都影响因子VII的水平。具有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冠状动脉疾病患者总体中的频率相似。在后一组中，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梗死的患者（通过卡方分析，启动子多态性存在的P = 0.008，R353Q多态性存在的P = 0.01）。具有A1A2或RQ基因型的患者发生心肌梗死的校正优势比为0.47（95%置信区间，0.27 - 0.81）。
结论：我们的研究结果表明，某些因子VII基因型在预防心肌梗死方面具有作用。这可能解释了为什么有些患者尽管存在严重的冠状动脉粥样硬化却没有发生心肌梗死。（《新英格兰医学杂志》2000年；343:774 - 80）（C）2000年，马萨诸塞州医学协会
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. (N Engl J Med 2000;343:774-80.) (C) 2000, Massachusetts Medical Society.