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Mutations in clotting factors and inflammatory bowel disease.

BACKGROUND: Patients with Crohn's disease (CD) and ulcerative colitis (UC) have a three- to fourfold greater risk of venous thrombosis compared with the general population. We aimed to determine if patients with CD and UC had a greater likelihood of mutations in genes that increase clotting risk, in a population-based case-control study.

METHODS: Subjects were drawn from the University of Manitoba IBD Research Registry and controls were drawn from Manitoba Health's administrative database. Cases (CD, N = 327; UC, N = 165) and controls (N = 412) underwent venipuncture. DNA was purified from whole blood. Genotypes for wild-type and common mutations that have been associated with venous thrombosis for each of Factor II (prothrombin) (G20210A), Factor V (G1691A:'Leiden'), methylenetetrahydrofolate reductase (MTHFR, C677T), and Factor XIII (val34leu) were assessed.

RESULTS: A total of 1.5% and 6.1% were heterozygous for Factor II and Factor V variants, respectively, without differences among cases and controls. Only one subject was homozygous for Factor V Leiden (and none were homozygous for Factor II mutation). Although some differences were observed among cases and controls in the prevalence of MTHFR C677T (decrease in mutant allele carriership in UC) and FXIII val34leu (increase in double mutant allele carriership in CD), these did not explain an excess risk of thrombosis. Age, sex, or disease phenotypes were not associated with prothrombotic genotypes.

CONCLUSIONS: While there was a slightly greater prevalence of Factor XIII mutation carriership in CD, we did not find that gene mutations for these four common factors could explain the greater risk of venous thrombosis in CD and UC.

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