Polymorphisms in prothrombotic genes and their impact on ischemic stroke in a Sardinian population

Genetic factors are involved in the individual predisposition to develop ischemic stroke (IS). In the present study we tested the role of the FactorVII G10976A and –C122T polymorphisms on the susceptibility to develop IS in a genetically homogenous and clinically well ascertained case-control study including 294 cases (median age 75 years; 176 males/118 females) and 286 controls (median age 73 years; 163 males/123 females) in Sardinia, Italy. In addition, we carried out an exploratory analysis with respect to other frequently studied polymorphisms of haemostatic factor genes:Factor II G20210A,FactorV G1691A,,Fibrinogen a -chain Thr312Ala, Fibrinogen β-chain –C148T, Factor XIII G185T, GPIIb/IIIa T1565C. Among all the genes tested, FVII –C122T showed a significant, independent contribution to IS predisposi tion both in crude and adjusted analyses (crude OR 1.52,95% CI 1.09–2.10, P=0.013; adjusted OR 1.48, 95% CI 1.04–2.09, P=0.028, respectively). Haplotype analyses revealed a conserved population structure with high linkage disequilibrium between both FVII mutations tested. Blood levels of FVII had an inverse relationship with the polymorphism involved. Apart from genetic influence, there was a significant role for hypertension (OR=1.7, 95% CI 1.19–2.43, P=0.003), hypercholesterolemia (OR=2.21, 95% CI 1.38–3.54, P=0.001) and atrial fibrillation (OR=1.66, 95% CI 1.06–2.58, P=0.026) on IS occurrence. In summary, we describe evidence for a possible direct association of FVII gene molecular variants with the occurrence of IS in a genetically homogenous human sample.