Iacoviello L, Di Castelnuovo A, De Knijff P, D'Orazio A, Amore C, Arboretti R, Kluft C, Benedetta Donati M
Department of Vascular Medicine and Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri, Santa Maria Imbaro, Italy.
N Engl J Med. 1998 Jan 8;338(2):79-85. doi: 10.1056/NEJM199801083380202.
High blood levels of coagulation factor VII are associated with a risk of ischemic vascular disease. Although factor VII levels may be genetically determined, the relation between genetic polymorphisms of factor VII, factor VII blood levels, and the risk of myocardial infarction has not been established.
We performed a case-control study of 165 patients with familial myocardial infarction (mean [+/-SD] age, 55+/-9 years) and 225 controls without a personal or family history of cardiovascular disease (mean age, 56+/-8 years). The polymorphisms involving R353Q and hypervariable region 4 of the factor VII gene were studied. Factor VII clotting activity and antigen levels were also measured.
Patients with the QQ or H7H7 genotype had a decreased risk of myocardial infarction (odds ratios, 0.08 [95 percent confidence interval, 0.01 to 0.9] and 0.22 [95 percent confidence interval, 0.08 to 0.63], respectively). For the R353Q polymorphism, the RR genotype was associated with the highest risk, followed by the RQ genotype and then by the QQ genotype (P<0.001). For the polymorphism involving hypervariable region 4, the combined H7H5 and H6H5 genotypes were associated with the highest risk, followed in descending order by the H6H6, H6H7, and H7H7 genotypes (P<0.001). Patients with the QQ or H7H7 genotype had lower levels of both factor VII antigen and factor VII clotting activity than those with the RR or H6H6 genotype. Patients with the lowest level of factor VII clotting activity had a lower risk of myocardial infarction than those with the highest level (odds ratio, 0.13; 95 percent confidence interval, 0.05 to 0.34).
Our findings suggest that certain polymorphisms of the factor VII gene may influence the risk of myocardial infarction. It is possible that this effect may be mediated by alterations in factor VII levels.
凝血因子VII的高血水平与缺血性血管疾病风险相关。尽管因子VII水平可能由基因决定，但因子VII基因多态性、因子VII血水平与心肌梗死风险之间的关系尚未确立。
我们对165例家族性心肌梗死患者（平均[±标准差]年龄，55±9岁）和225例无心血管疾病个人或家族史的对照者（平均年龄，56±8岁）进行了一项病例对照研究。研究了因子VII基因涉及R353Q和高变区4的多态性。还测量了因子VII凝血活性和抗原水平。
QQ或H7H7基因型患者发生心肌梗死的风险降低（优势比分别为0.08[95%置信区间，0.01至0.9]和0.22[95%置信区间，0.08至0.63]）。对于R353Q多态性，RR基因型与最高风险相关，其次是RQ基因型，然后是QQ基因型（P<0.001）。对于涉及高变区4的多态性，H7H5和H6H5基因型组合与最高风险相关，按风险从高到低依次为H6H6、H6H7和H7H7基因型（P<0.001）。QQ或H7H7基因型患者的因子VII抗原和因子VII凝血活性水平均低于RR或H6H6基因型患者。因子VII凝血活性水平最低的患者发生心肌梗死的风险低于水平最高的患者（优势比，0.13；95%置信区间，0.05至0.34）。
我们的研究结果表明，因子VII基因的某些多态性可能影响心肌梗死风险。这种效应可能由因子VII水平的改变介导。
