Elliott C G, Leppert M F, Alexander G J, Ward K, Nelson L, Pietra G G
Dept of Medicine, LDS Hospital, University of Utah School of Medicine, Salt Lake City 84143, USA.
Eur Respir J. 1998 Nov;12(5):1177-80. doi: 10.1183/09031936.98.12051177.
Substantial evidence suggests that thrombosis contributes to the pathogenesis of primary pulmonary hypertension (PPH). An abnormal factor V (factor V Leiden) may contribute to thrombosis in the pulmonary microcirculation of PPH patients. A point mutation in which adenine is substituted for guanine at nucleotide 1691 (1691A) alters factor V so that it resists cleavage by activated protein C. Heterozygosity for the 1691A mutation is more common (2-8%) in Caucasian Europeans and Americans than in Africans (1%) and Asians (<1%). The aim of the study was to examine the prevalence of the mutation that codes for factor V Leiden in individuals with PPH. We identified 42 Caucasians diagnosed with PPH. We extracted deoxyribonucleic acid (DNA) from whole blood and assayed DNA samples for the point mutation (1691 A) that codes for factor V Leiden. One out of 42 (2.4%; 95% confidence interval=0.1-12.6) Caucasians diagnosed with PPH was heterozygous for the normal 1691G and mutant 1691A allele. All 10 individuals with familial PPH were homozygous for the normal 1691G allele. The prevalence of heterozygosity for the 1691A allele and the normal 1691G allele does not differ from that observed in reference (control) populations. The low prevalence of the 1691A mutation among individuals diagnosed with primary pulmonary hypertension provides evidence that factor V Leiden does not contribute to the pathogenesis of the disease in most patients.
大量证据表明,血栓形成在原发性肺动脉高压(PPH)的发病机制中起作用。异常的因子V(因子V莱顿)可能导致PPH患者肺微循环中的血栓形成。在核苷酸1691处腺嘌呤取代鸟嘌呤的点突变改变了因子V,使其抵抗活化蛋白C的切割。1691A突变的杂合子在白种欧洲人和美国人中比在非洲人(1%)和亚洲人(<1%)中更常见(2 - 8%)。本研究的目的是检测原发性肺动脉高压患者中编码因子V莱顿的突变的患病率。我们确定了42名被诊断为PPH的白种人。我们从全血中提取脱氧核糖核酸(DNA),并检测DNA样本中编码因子V莱顿的点突变(1691A)。42名被诊断为PPH的白种人中有1人(2.4%;95%置信区间 = 0.1 - 12.6)是正常1691G和突变1691A等位基因的杂合子。所有10名家族性PPH患者均为正常1691G等位基因的纯合子。1691A等位基因和正常1691G等位基因的杂合子患病率与参考(对照)人群中观察到的患病率没有差异。在被诊断为原发性肺动脉高压的个体中1691A突变的低患病率表明,因子V莱顿在大多数患者的疾病发病机制中不起作用。