Correlation of FXII 46CT polymorphism with FXII activity and risk of thrombotic diseases

Background and ObjectivesThere are a number of well-characterized genetic defects that lead to increased risk of thrombosis. Results from previous studies have indicated that plasma FXII activity levels are strongly determined by a 46CT polymorphism in the FXII gene. In the present study, the risk of thrombophilic diseases related to this polymorphism was investigated. Materials and MethodsOne hundred sixty individuals were included in this case-control study: 120 patients diagnosed with thrombophilia and 40 age-gender-matched controls. For each subject, FXII activity level was measured using a one-step clotting assay, and 46CT polymorphism was genotyped using a PCR-RFLP techniques. ResultsIn this study, FXII activity < 68% was associated with an increased risk of thrombophilia with an adjusted odds ratio of 4.75 (CI 95% = 1.07 – 21.1). In CT and TT genotypes, the adjusted odds ratios were respectively 1.81 (CI 95% = 0.83-3.94) and 2.17 (CI 95% = 0.45-10.7) for thrombotic patients compared with the controls. Thus, we did not find any association of the mutated T allele in the heterozygous or homozygous state with an increased risk of thrombophilia. ConclusionsThis study showed that 46CT is a strong determinant of FXII activity. However, there was not any association between mutant T allele and increased risk of thrombosis. Therefore, it was speculated that reduced FXII activity is not the cause but the outcome of thrombosis. In other words, lower FXII activity is not a risk factor for thrombosis, rather it simply represents a risk marker.