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

Abstract: Genetic factors are involved in the individual predisposition to develop ischemic stroke (IS). In the present study we tested the role of the FactorVII G 10976A and -CI22T 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 G202 10A, FactorV G 169 1 A,, Fibrinogen (x-chain Thr312Ala, Fibrinogen beta-chain -C148T, Factor XIII G185T, GPIlb/IIIa T1565C. Among all the genes tested, FVII -C122T showed a significant, independent contribution to IS predisposition both in crude and adjusted analyses (crude OR 1.52,95% Cl 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% Cl 1.19-2.43, P=0.003), hypercholesterolemia (OR=2.21, 95% Cl 1.38-3.54, P=0.001) and atrial fibrillation (OR=1.66, 95% Cl 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.