title: Factor XIII-A subunit Val34Leu polymorphism in fatal atherothrombotic ischemic stroke.
abstract: Factor XIII (FXIII) is a regulator of fibrinolysis and clot firmness. Val34Leu polymorphism of its potentially active A subunit (FXIII-A) leads to faster activation of FXIII, influences clot structure and provides a moderate protection against coronary artery disease. The effect of FXIII-A Val34Leu polymorphism on the risk of atherothrombotic ischemic stroke (AIS) has been investigated in a few studies with contradictory results. In all previous studies, only patients surviving AIS were enrolled and sex-specific effects were not explored. In this retrospective multicenter cohort, we investigated the effect of FXIII-A Val34Leu polymorphism on the risk of fatal AIS in women and men. DNA isolation and genetic determinations in the case of 316 patients who died of AIS were carried out on paraffin-embedded tissue specimens. Genetic analyses for population controls, patients with history of AIS and sex-matched controls were performed on extracted genomic DNA from peripheral blood leukocytes. The prevalence of homozygous wild-type, and heterozygous genotypes, Leu34 carriers and Leu34 allele was not different significantly between the patients with fatal AIS and their respective controls. Logistic regression analysis with age as co-variant demonstrated that in women, homozygous presentation of Leu34 allele represented a more than three-fold increased risk of AIS with fatal outcome. The results demonstrate that FXIII-A Val34Leu polymorphism does not influence the occurrence of AIS, but has an effect on the severity of its outcome. This effect is sex-specific and in homozygous women, the prothrombotic/antifibrinolytic effects of FXIII-A Val34Leu polymorphism seem to prevail.
authors.affiliation: aMTA-DE Vascular Biology, Thrombosis and Hemostasis Research Group, Hungarian Academy of Sciences, University of Debrecen, Medical and Health Science Center, Debrecen bLabPharm Kft, Sátoaljaújhely cDepartment of Pathology, Diósgyori Vasgyári Hospital, Miskolc dDepartment of Neurology, Hetényi Géza Hospital, Szolnok eClinical Research center, University of Debrecen, Medical and Health Science Center fDepartment of Internal medicine, University of Debrecen, Medical and Health Science Center, Debrecen, Hungary.
authors.forename: Amir-Houshang
authors.initials: AH
authors.lastname: Shemirani
authors.forename: Bálint
authors.initials: B
authors.lastname: Antalfi
authors.forename: Endre
authors.initials: E
authors.lastname: Pongrácz
authors.forename: Zoltán András
authors.initials: ZA
authors.lastname: Mezei
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Bereczky
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Csiki
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002545:Brain Ischemia / Q000097:blood / Q000235:genetics*; D015331:Cohort Studies; D005176:Factor XIII / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D002537:Intracranial Arteriosclerosis / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000235:genetics*
chemical_list: D005176:Factor XIII