Ridker P M, Hennekens C H, Lindpaintner K, Stampfer M J, Eisenberg P R, Miletich J P
Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215-1204.
N Engl J Med. 1995 Apr 6;332(14):912-7. doi: 10.1056/NEJM199504063321403.
A specific point mutation in the gene coding for coagulation factor V is associated with resistance to degradation by activated protein C, a recently described abnormality of coagulation that may be associated with an increased risk of venous thrombosis. Whether this mutation also predisposes patients to arterial thrombosis is unknown, as is the value of screening for the mutation in order to define the risk of venous thrombosis among unselected healthy people.
Among 14,916 apparently healthy men in the Physicians' Health Study who provided base-line blood samples, 374 had myocardial infarctions, 209 had strokes, and 121 had deep venous thrombosis, pulmonary embolism, or both, during a mean follow-up of 8.6 years. We determined whether a mutation at nucleotide position 1691 of the factor V gene was present or absent in these 704 men and in an equal number of matched participants who remained free of vascular disease.
The prevalence of heterozygosity for the mutation among men who had myocardial infarctions (6.1 percent, P = 0.9) or strokes (4.3 percent, P = 0.4) was similar to that among men who remained free of vascular disease (6.0 percent). However, the prevalence of the mutation was significantly higher among men who had venous thrombosis, pulmonary embolism, or both (11.6 percent, P = 0.02). In adjusted analyses, the relative risk of venous thrombosis among men with the mutation was 2.7 (95 percent confidence interval, 1.3 to 5.6; P = 0.008). This increased risk was seen with primary venous thrombosis (relative risk, 3.5; 95 percent confidence interval, 1.5 to 8.4; P = 0.004) but not with secondary venous thrombosis (relative risk, 1.7; 95 percent confidence interval, 0.6 to 5.3; P = 0.3), and it was most apparent among older men. Specifically, the prevalence of the mutation among men over the age of 60 in whom primary venous thrombosis developed was 25.8 percent (relative risk, 7.0; 95 percent confidence interval, 2.6 to 19.1; P < 0.001).
In a large cohort of apparently healthy men, the presence of a specific point mutation in the factor V gene was associated with an increased risk of venous thrombosis, particularly primary venous thrombosis. The presence of the mutation was not associated with an increased risk of myocardial infarction or stroke. This mutation appears to be the most common inherited factor thus far recognized that predisposes patients to venous thrombosis.
凝血因子V编码基因中的一种特定点突变与对活化蛋白C降解的抵抗有关，活化蛋白C是一种最近描述的凝血异常，可能与静脉血栓形成风险增加有关。这种突变是否也使患者易患动脉血栓形成尚不清楚，同样，在未选择的健康人群中筛查该突变以确定静脉血栓形成风险的价值也不清楚。
在医师健康研究中14916名表面健康的男性中，他们提供了基线血样，在平均8.6年的随访期间，374人发生心肌梗死，209人发生中风，121人发生深静脉血栓形成、肺栓塞或两者皆有。我们确定了这704名男性以及同等数量未患血管疾病的匹配参与者中，因子V基因核苷酸位置1691处是否存在突变。
发生心肌梗死的男性（6.1%，P = 0.9）或中风的男性（4.3%，P = 0.4）中该突变杂合子的患病率与未患血管疾病的男性（6.0%）相似。然而，发生静脉血栓形成、肺栓塞或两者皆有的男性中该突变的患病率显著更高（11.6%，P = 0.02）。在多因素分析中，有该突变的男性发生静脉血栓形成的相对风险为2.7（95%可信区间，1.3至5.6；P = 0.008）。这种风险增加在原发性静脉血栓形成中可见（相对风险，3.5；95%可信区间，1.5至8.4；P = 0.004），而在继发性静脉血栓形成中未见（相对风险，1.7；95%可信区间，0.6至5.3；P = 0.3），并且在老年男性中最为明显。具体而言，60岁以上发生原发性静脉血栓形成的男性中该突变的患病率为25.8%（相对风险，7.0；95%可信区间，2.6至19.1；P < 0.001）。
在一大群表面健康的男性中，因子V基因中一种特定点突变的存在与静脉血栓形成风险增加有关，尤其是原发性静脉血栓形成。该突变的存在与心肌梗死或中风风险增加无关。这种突变似乎是迄今为止公认的使患者易患静脉血栓形成的最常见遗传因素。
