Polymorphism FXII 46C>T and cardiovascular risk: additional data from Spanish and Tunisian patients

A Transmission Disequilibrium Test (TDT) based on 101 family trios from Barcelona with one offspring affected by ischemic heart disease and a classical case-control study based on 76 patients with IHD and 118 healthy individuals from North and Centre-South Tunisia were conducted. Subjects were genotyped for 46C>T and data were analyzed accordingly, revealing no association in any of the two samples (TDT: P = 0.16, relative risk 1.17; case-control study: P = 0.59, odds ratio 1.36).The results suggest that 46C>T is not a risk factor for ischemic heart disease in any of the two analyzed samples and therefore the polymorphism seems not to be a universal risk factor for cardiovascular diseases.The gene of coagulation Factor (F) XVII has been repeatedly analysed in many epidemiological studies on cardiovascular (CV) genetic risk with controversial results. It has been reported that FXII plasma levels exhibit a 67% of heritability and that these levels are strongly determined by F12 gene variants.[1] Although low FXII plasma levels have been reported to affect the development of CV diseases, it has been recently proposed that, rather than the cause of thrombosis, these low levels are actually the result of it. [2,3]A highlighted F12 polymorphism is the 46C>T transition. It seems that 46C>T affects the translation efficiency, leading to reduced FXII plasma levels.[4] This polymorphism (with allele frequencies 0.8/0.2 in Caucasians) accounts for 40% of the variance in FVII activity in a Spanish Mediterranean population and seems to fit a log additive model of inheritance with an allele dose-dependent effect.[1,4]Previous genetic association studies between 46C>T and CV risk showed that genotype T/T increases significantly the risk for venous thrombosis, ischemic stroke and acute coronary artery disease in a Spanish population. [5-7] The odds ratio in acute coronary artery disease was estimated around 4.8.[7] Conversely, there are also studies that either do not detect geneti