An unknown genetic defect increases venous thrombosis risk, through interaction with protein C deficiency.

University of Utah, Department of Human Genetics, Salt Lake City, UT 84112-5330, USA.
The American Journal of Human Genetics (Impact Factor: 10.99). 09/1998; 63(2):569-76. DOI: 10.1086/301947
Source: PubMed

ABSTRACT We used two-locus segregation analysis to test whether an unknown genetic defect interacts with protein C deficiency to increase susceptibility to venous thromboembolic disease in a single large pedigree. Sixty-seven pedigree members carry a His107Pro mutation in the protein C gene, which reduces protein C levels to a mean of 46% of normal. Twenty-one carriers of the mutation and five other pedigree members had verified thromboembolic disease. We inferred the presence in this pedigree of a thrombosis-susceptibility gene interacting with protein C deficiency, by rejecting the hypothesis that the cases of thromboembolic disease resulted from protein C deficiency alone and by not rejecting Mendelian transmission of the interacting gene. When coinherited with protein C deficiency, the interacting gene conferred a probability of a thrombotic episode of approximately 79% for men and approximately 99% for women, before age 60 years.

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