Influence of three potential genetic risk factors for thrombosis in 43 families carrying the factor VArg 506 to Gln mutation

The factor V (FV) Arg 506 to Gln mutation is the most common abnormality ob served in familial thrombophilia. Many studies have shown that its clinical expression differs among families and among carriers. Some thrombotic pati ents carry an additional genetic risk factor such as protein C, protein S o r antithrombin deficiency. We sought to identify other genetic risk factors potentially favouring expression of the thrombotic phenotype in 370 member s of 43 families with the FV Arg 506 to Gln mutation. We analysed three can didate polymorphisms in genes involved in the PC anticoagulant pathway, con sisting of two polymorphic sites in the 5' non-transcribed region of the PC gene, -1654 C/T and -1641 A/G, with three known combinations (TA, CA and C G) that influence the protein C plasma level; one polymorphic site (4070 A/ G) in exon 13 of the FV gene, which influences the plasma factor V concentr ation, and one polymorphic site (677 C/T) in the methylenetetrahydrofolate reductase gene, which is often associated with moderate hyperhomocysteinaem ia. The distribution of these different polymorphisms was similar in patien ts with a history of thrombosis and those who remained asymptomatic, ruling out the possibility that each of these polymorphisms alone can play a role in the onset of thrombosis in carriers of the FV Arg 506 to Gln mutation.