Association of a common polymorphism in the factor XIII gene with venous thrombosis

We have shown an association between a common mutation in the factor XIII a -subunit gene, coding for an amino acid change, 3 amino acids from the thro mbin activation site (factor XIII Val34Leu) that may protect against myocar dial infarction and predisposes to intracranial hemorrhage. To investigate the possible role of factor XIII Val34Leu in the pathogenesis of venous thr omboembolism (VTE) and potential interactions with factor V Leiden (FV:Q(50 6)) and prothrombin G --> A 20210, we studied 221 patients with a history o f VTE and 254 healthy controls. Patients with VTE showed an increased frequ ency of the FXIII Val/Val genotype (63% v 49%) and a lower frequency of the Val/Leu genotype (31% v 42%) than controls (P = .007). FV:Q(506) heterozyg otes were more frequent in VTE patients (11%) than controls (5%; P = .04). The prothrombin G --> A 20210 mutation was present in only 3 patients and n o controls (P = .10), In a logistic regression model for a history of VTE, the odds ratio (95% confidence interval) for FXIII Val/Leu or Leu/Leu genot ype was 0.63 (0.38 to 0.82) and for possession of FV:Q(506) 2.40 (1.17 to 4 .90). There was no evidence for an interaction between factor XIII Val34Leu genotype and FV:Q(506), prothrombin G --> A 20210, sex, or age. It is conc luded that possession of the Leu allele at factor XIII Val34Leu is protecti ve against deep venous thrombosis. (C) 1999 by The American Society of Hema tology.