RGD Reference Report - Association after linkage analysis indicates that homozygosity for the 46C-->T polymorphism in the F12 gene is a genetic risk factor for venous thrombosis. - Rat Genome Database

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Association after linkage analysis indicates that homozygosity for the 46C-->T polymorphism in the F12 gene is a genetic risk factor for venous thrombosis.

Authors: Tirado, I  Soria, JM  Mateo, J  Oliver, A  Souto, JC  Santamaria, A  Felices, R  Borrell, M  Fontcuberta, J 
Citation: Tirado I, etal., Thromb Haemost. 2004 May;91(5):899-904.
RGD ID: 11041808
Pubmed: (View Article at PubMed) PMID:15116249
DOI: Full-text: DOI:10.1160/TH03-10-0620

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.

Annotation

Disease Annotations    
Venous Thrombosis  (IAGP,ISO)

Objects Annotated

Genes (Rattus norvegicus)
F12  (coagulation factor XII)

Genes (Mus musculus)
F12  (coagulation factor XII (Hageman factor))

Genes (Homo sapiens)
F12  (coagulation factor XII)


Additional Information