Contribution of the -455G/A polymorphism at β-fibrinogen gene and of the Leiden mutation to hemorheological parameters in ischemic stroke patients

Issue title: Selected Proceedings of the European Society for Clinical Hemorheology (E.S.C.H.), 26–29 June, 2005, Siena, Italy

Article type: Research Article

Authors: Pongrácz, Endre^; | Andrikovics, Hajnalka | Csornai, Márta | Bernát, Iván S. | Nagy, Zoltán

Affiliations: Central Hospital of Home Office, Neurological Department, Budapest, Hungary | National Institute of Hemathology, Department of Molecular Genetics, Budapest, Hungary | County Hospital, Department of Neurology, Kecskemét, Hungary | Central Military Hospital, Department of Cardiology, Budapest, Hungary | National Stroke Centre, Semmelweis University, Budapest, Hungary

Note: [] Corresponding author: Endre Pongrácz, MD, Central Hospital of Home Office, Department of Neurology, Stroke Unit, Városligeti fasor 9-13, H-1071, Budapest, Hungary. Tel.: +36 1 462 5637; Fax: +36 1 462 5611; E-mail: [email protected].

Abstract: The concentration of plasma fibrinogen (FIB) is an important factor in the coagulation cascade and also in the determination of blood and plasma viscosity depending on both genetic and acquired factors. The -455G/A polymorphism of the β-FIB gene is connected to the plasma concentration of FIB but the effect of Leiden mutation on hemorheological parameters is unclear. The two genetic polymorphisms were studied by polymerase chain reaction in healthy subjects and ischemic stroke cohort and the effects on the concentration of plasma FIB, whole blood and plasma viscosity of patients as well. A total of 278 ischemic stroke patients and 173 control subjects were enrolled. Marcro-rheological parameters as plasma FIB concentration, whole blood viscosity (90 sec−1 shear rate) and plasma viscosity have been measured also in the subgroup of young (age<50 years) and in a subgroup of non-smoker patients. Results: No significant difference was found in the prevalency of H1/H2 genotype between controls and cases in pooled stroke group OR 0.95 (95% CI: 0.47–1.27), however H2/H2 genotype frequency was increased in young subgroup of patients (OR: 1.66 95% CI: 0.52–5.25). Plasma FIB concentration was increased both in the total cohort (p<0.05) and in the non-smoker subgroup (p<0.03) of patients carried H2/H2 as compared to H1/H1 genotype and the prevalence was increased in the group of patients having plasma FIB concentration >4 g/l (p<0.05). The whole blood viscosity was elevated in the H2/H2 group as compared to the group carrying wild type (p<0.03). A tendency of increased plasma viscosity in the group of patients with H2/H2 genotype as compared to wild type was found (p=0.07). Leiden mutation prevalence showed an increased risk OR: 1.67 (95% CI: 0.75–3.70) in the young patients group as compared to controls. In patients who have had the highest plasma viscosity, higher frequency of Leiden mutation was detected as compared to wild type, in total group (p=0.01), in young patients (p=0.03) and in subgroup of non-smoker patients (p=0.05). Conclusions: Our findings support the notion that the homozigous variant of β-FIB gene can raise both plasma FIB concentration and whole blood viscosity. Leiden mutation connected to the elevation of plasma viscosity could demonstrate a new pathway of increased thrombophylic potential in ischemic stroke patients.

Keywords: Ischemic stroke, genetic polymorphisms, -445 β-fibrinogen, Leiden mutation, blood viscosity, plasma viscosity, hemorheology

Journal: Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 75-82, 2006