Genetic factors are involved in the individual predisposition to develop ischemic stroke (IS). In the present study we tested the role of the Factor VII 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, Factor V G1691A,, Fibrinogen α-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 predisposition 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.
- Coagulation factors
ASJC Scopus subject areas