title: 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 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 alpha-chain Thr312Ala, Fibrinogen beta-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.
authors.affiliation: IRCCS Neuromed, Localita' Camerelle, 86077 Pozzilli (Is), Italy. rubattu.speranza@neuromed.it
authors.forename: Speranza
authors.initials: S
authors.lastname: Rubattu
authors.forename: Emanuele
authors.initials: E
authors.lastname: Di Angelantonio
authors.forename: Dorothea
authors.initials: D
authors.lastname: Nitsch
authors.forename: Bruna
authors.initials: B
authors.lastname: Gigante
authors.forename: Bastianina
authors.initials: B
authors.lastname: Zanda
authors.forename: Rosita
authors.initials: R
authors.lastname: Stanzione
authors.forename: Anna
authors.initials: A
authors.lastname: Evangelista
authors.forename: Angelo
authors.initials: A
authors.lastname: Pirisi
authors.forename: Giulio
authors.initials: G
authors.lastname: Rosati
authors.forename: Massimo
authors.initials: M
authors.lastname: Volpe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001779:Blood Coagulation Factors / Q000235:genetics*; D002545:Brain Ischemia / Q000097:blood / Q000235:genetics; D016022:Case-Control Studies; D005167:Factor VII / Q000235:genetics / Q000378:metabolism; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007558:Italy; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D020521:Stroke / Q000097:blood* / Q000235:genetics*
chemical_list: D001779:Blood Coagulation Factors; D005167:Factor VII