Zöller B, Dahlbäck B
Department of Clinical Chemistry, University of Lund, Malmö General Hospital, Sweden.
Lancet. 1994 Jun 18;343(8912):1536-8. doi: 10.1016/s0140-6736(94)92940-8.
Resistance to activated protein C (APC) is a major cause of familial thrombophilia, and can be corrected by an anticoagulant activity expressed by purified factor V. We investigated linkage between APC resistance and the factor V gene in a large kindred with familial thrombophilia. Restriction fragment length polymorphisms in exon 13 of the factor V gene were informative in 14 family members. The 100% linkage between factor V gene polymorphism and APC resistance strongly suggested a factor V gene mutation as a cause of APC resistance. A point mutation changing Arg506 in the APC cleavage site to a Gln was found in APC resistant individuals. These results suggest factor V gene mutation to be the most common genetic cause of thrombophilia.
对活化蛋白C（APC）的抵抗是家族性血栓形成倾向的主要原因，并且可以通过纯化的因子V所表达的抗凝活性来纠正。我们在一个患有家族性血栓形成倾向的大家系中研究了APC抵抗与因子V基因之间的连锁关系。因子V基因第13外显子中的限制性片段长度多态性在14名家庭成员中具有信息性。因子V基因多态性与APC抵抗之间100%的连锁关系强烈提示因子V基因突变是APC抵抗的原因。在APC抵抗个体中发现了一个点突变，该突变将APC裂解位点的精氨酸506变为谷氨酰胺。这些结果提示因子V基因突变是血栓形成倾向最常见的遗传原因。
