Ridker P M, Hennekens C H, Miletich J P
Divisions of Preventive Medicine and Cardiovascular Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Circulation. 1999 Mar 2;99(8):999-1004. doi: 10.1161/01.cir.99.8.999.
A single base pair mutation in the prothrombin gene has recently been identified that is associated with increased prothrombin levels. Whether this mutation increases the risks of arterial and venous thrombosis among healthy individuals is controversial.
In a prospective cohort of 14 916 men, we determined the prevalence of the G20210A prothrombin gene variant in 833 men who subsequently developed myocardial infarction, stroke, or venous thrombosis (cases) and in 1774 age- and smoking status-matched men who remained free of thrombosis during a 10-year follow-up (control subjects). Gene sequencing was used to confirm mutation status in a subgroup of participants. Overall, carrier rates for the G20210A mutation were similar among case and control subjects; the relative risk of developing any thrombotic event in association with the 20210A allele was 1.05 (95% CI, 0.7 to 1.6; P=0.8). We observed no evidence of association between mutation and myocardial infarction (RR=0.8, P=0.4) or stroke (RR=1.1, P=0.8). For venous thrombosis, a modest nonsignificant increase in risk was observed (RR=1.7, P=0.08) that was smaller in magnitude than that associated with factor V Leiden (RR=3.0, P<0. 001). Nine individuals carried both the prothrombin mutation and factor V Leiden (5 controls and 4 cases). One individual, a control subject, was homozygous for the prothrombin mutation.
In a large cohort of US men, the G20210A prothrombin gene variant was not associated with increased risk of myocardial infarction or stroke. For venous thrombosis, risk estimates associated with the G20210A mutation were smaller in magnitude than risk estimates associated with factor V Leiden.
最近发现凝血酶原基因中的一个单碱基对突变与凝血酶原水平升高有关。该突变是否会增加健康个体发生动脉和静脉血栓形成的风险仍存在争议。
在一项对14916名男性的前瞻性队列研究中，我们确定了833名随后发生心肌梗死、中风或静脉血栓形成的男性（病例组）以及1774名年龄和吸烟状况相匹配且在10年随访期间未发生血栓形成的男性（对照组）中凝血酶原基因G20210A变异的患病率。基因测序用于确认部分参与者的突变状态。总体而言，病例组和对照组中G20210A突变的携带率相似；与20210A等位基因相关的发生任何血栓形成事件的相对风险为1.05（95%CI，0.7至1.6；P=0.8）。我们未观察到突变与心肌梗死（RR=0.8，P=0.4）或中风（RR=1.1，P=0.8）之间存在关联的证据。对于静脉血栓形成，观察到风险有适度的非显著性增加（RR=1.7，P=0.08），其幅度小于与因子V莱顿突变相关的风险增加幅度（RR=3.0，P<0.001）。9名个体同时携带凝血酶原突变和因子V莱顿突变（5名对照者和4名病例）。一名对照者为凝血酶原突变纯合子。
在美国男性的一个大型队列中，凝血酶原基因G20210A变异与心肌梗死或中风风险增加无关。对于静脉血栓形成，与G20210A突变相关的风险估计幅度小于与因子V莱顿突变相关的风险估计幅度。
