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

UNLABELLED: 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 beta-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 beta-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.

[Significance of Factor V gene A506G mutation (Leiden) in the pathogenesis of ischemic stroke]. / Van-e jelentósége az V. faktor gén A506G (Leiden-féle) mutációjának ischaemiás stroke esetén?

BACKGROUND: There are conflicting data about the role of Leiden mutation in the pathogenesis of cerebral arterial thrombosis. In order to obtain relevant data, authors investigated the prevalence of factor V Leiden (A506G) both in healthy subjects and in a subgroup of ischaemic stroke patients. MATERIAL AND METHODS: Blood samples of 171 healthy persons and 254 ischaemic stroke patients were examined by PCR method for Leiden mutation. Ischaemic lesions in the stroke group were documented by CT or MRI. A routine questionnaire was used to study the family history of vascular events (hypertension, diabetes, POAD, stroke, myocardial infarction) of patients. Conventional vascular risk factors of patients were also documented. RESULTS: The prevalence of Leiden mutation was 7.2% in healthy persons and 11.9% in stroke patients. The OR for 254 patient was 1.45 (0.71-2.97). In the subgroup of young patients: age < 50 (n = 134) the OR was 1.67 (0.75-3.70) and in the elderly patients group: age > 50 (n = 120) the OR was 1.21 (0.50-2.89). In the family history of stroke patients having Leiden mutation (hetero- and homozygosity) the stroke prevalence was higher (p = 0.01). In the ischaemic stroke group, age < 50 with polymorphism a tight correlation with hyperlipidaemia (p = 0.03) was found. In the group of age < 50 with heterozygosity for Leiden, a lower plasma fibrinogen concentration (p = 0.02) was found. The polymorphism showed no correlation with the hypertension, hyperuricaemia, migraine, diabetes mellitus, smoking, alcohol consumption and CDS status of patients. CONCLUSION: When comparing stroke patients to control population there is no significant increase in the frequency of Leiden mutation. Leiden mutation together with hyperlipidaemia and stroke in the family history results in high risk for ischaemic stroke in young patients.

[Investigation of insertion/deletion polymorphism of the ACE gene in stroke patients]. / Stroke-betegek insertiós-deletiós ACE-gén-polimorfizmusának vizsgálata.

INTRODUCTION: This is the first Hungarian paper on the insertion/deletion polymorphism of ACE gene in stroke patients. According to literature data, the role of this polymorphism is controversial in the pathogenesis of stroke. The aim was to study the prevalence of the polymorphism in healthy persons and in stroke patients. PATIENTS AND METHODS: Blood samples from 173 unrelated healthy donors and 253 stroke patients were investigated by polymerase chain reaction (PCR). PrevIous stroke was documented by CT or MRI and CDS. A routine questionnaire was used to study previous vascular events and the risk profile of patients. RESULTS: I/I allele was found in 20%, I/D 52% and D/D 28% in the healthy group. Prevalence of the pathologic D/D allele did not differ between healthy and patients group (28% and 27%, OR: 0.88, and in subgroup age under 50 years OR: 1.00). No correlation was found between D/D and conventional risk profile but a positivE correlation was found in young patients having D/D and hyperlipidemia (p < 0.05) and hyperfibrinogenemia (p < 0.05). D/D prevalence was found higher in patients with family anamnesis of myocardial infarction (p < 0.05). Very low prevalence of D/D allele was found in cardiogen embolic group (p > 0.05). CONCLUSIONS: The ACE polymorphism does not seem to be an independent risk factor for stroke. However, in young stroke patients with D/D allele, hyperlipidemia and/or hyperfibrinogenemia present very high risk for stroke.

[Genetics of blood coagulation in young stroke patients]. / Véralvadási genetika fiatalkori stroke-ban.

BACKGROUND AND PURPOSE: The classical risk factors did not explain all the possible etiology of cerebral stroke. Genetic polymorphisms responsible for thrombophilia were implicated recently as risk factors of stroke. In this genetico-epidemiological study the author's aim was to analyse the tendency of genetic polymorphisms to cluster in a cohort of young and elderly stroke patients and in healthy subjects in Hungary. METHODS: 253 patients with stroke were compared with 173 healthy blood donors on the basis of genetic polymorphisms of platelet GP IIb/IIIa receptor (33 LeuPro), prothrombin gene G20210A, Factor V Leiden mutation, ACE I/D, methylenetetrahydrofolate reductase (MTHFR) and beta fibrinogen gene G455A. These data were acquired using PCR. Questionnaires were used to investigate the family history and to determine the risk factor profile. The subtypes of stroke were analysed in a stroke cohort grouped according to different polymorphisms. RESULTS: An increased frequency of GP IIIa heterozygosity was found as compared to a West-European stroke cohort (31% versus 19%). The prothrombin gene variant (2.9% European and 4.8% in Hungary) was also found to increase in frequency. In young stroke patients (age < 50) compared with control subjects the odds ratios were higher: in prothrombin gene (OR: 4.9), in Leiden mutation (OR: 1.67), in fibrinogen gene (OR: 1.64) and in MTHFR(+/+) (OR: 1.58). Clustering of two polymorphisms could only be detected in young patients. These clustering polymorphisms were GP IIb/IIIa with prothrombin G20210A variant (OR: 6.74, 95% CI 1.1-18.2) and prothrombin gene variant with MTHFR (OR: 5.3, CI95 1.2-8.3). CONCLUSION: Selected and clustered genetic polymorphisms of haemostatic factors could be responsible for the high stroke morbidity in Central Europe. The presence and clustering tendency of these factors have been described in young stroke victims.

[Issues in the care of stroke patients]. / A stroke-betegek gondozásának problémái.

All patients having had stroke or TIA require special post-hospital care, being mainly the task of general practitioners. The number of patients surviving stroke in Hungary is approximately 30,000/year. An important focus of care is secondary prevention: antithrombotic treatment and risk factors reduction. In case of residual signs of stroke, rehabilitation must also be organized and supported by the general practitioner. Medical conditions of cerebrovascular patients requiring special care demand are reviewed by the author. In this respect, some post-stroke conditions like dementia and depression require extra attention.