ca427a27-e97e-4769-bc30-4fa25f7acb37
title
Association after linkage analysis indicates that homozygosity for the  46C-->T  polymorphism in the  F12  gene is a genetic risk factor for venous thrombosis.
9aae372a-f040-4336-ae34-14b8606bf5cb
abstract
In a family-based study called GAIT (Genetic Analysis of Idiopathic Thrombophilia) that included a genome-wide scan we demonstrated that a polymorphism ( 46C-->T ) in the  F12  locus jointly influences variability of plasma  (Factor XII) FXII  levels and susceptibility to thrombotic disease. It then became germane to determine the prevalence of the  46C-->T  polymorphism and its relative risk of thrombotic disease. We followed up evidence for genetic linkage with a case-control study, including 250 unrelated consecutive Spanish patients suffering from venous thrombotic disease and 250 Spanish subjects matched for sex and age as a controls. We measured  FXII  levels and genotyped the  46C-->T  polymorphism, as well as a number of classical risk factors for thrombotic disease.We confirmed that individuals with different genotypes for this polymorphism showed significant differences in their  FXII  levels. Most importantly, the mutated T allele in the homozygous state (genotype T/T) was associated with an increased risk of thrombosis (adjusted OR of 4.82; 95% CI 1.5-15.6), suggesting that the polymorphism itself is an independent risk factor for venous thromboembolism. This study confirms that the  46C-->T  polymorphism is a genetic risk factor for venous thrombosis in the Spanish population. In addition, our results confirm that a genome-wide scan coupled with a classical case-control association study is an extremely valuable approach to identify DNA variants that affect complex diseases.