Lamia M'barek1,2, Salma Sakka1, Fatma Megdiche3,4, Nouha Farhat1, Khadija Maalla1, Dhaker Turki1, Sawsan Feki5, Ahmed Rebai6, Mariem Dammak1, Choumous Kallel3,4, Chokri Mhiri1,2. 1. Laboratory of Neurogenetics, Parkinson's Disease and Cerebrovascular Disease (LR-12-SP-19), University of Sfax, Sfax, Tunisia. 2. Clinical Investigation Center (CIC), Habib Bourguiba University Hospital, Sfax, Tunisia. 3. Laboratory of Hematology, Habib Bourguiba University Hospital, Sfax, Tunisia. 4. Faculty of Pharmacy, University of Monastir, Monastir, Tunisia. 5. Autoimmunity, Cancer and Immunogenetics" Research Laboratory (LR18SP12), Immunology Department, Habib Bourguiba Hospital, University of Sfax, Sfax, Tunisia. 6. Molecular and Cellular Screening Process Laboratory, Centre of Biotechnology of Sfax, Sfax, Tunisia.
Abstract
BACKGROUND: The involvement of traditional risk factors and combined genetic markers of recurrent arterial ischemic stroke (AIS) in adults remains unclear. OBJECTIVE: This study aims to determine significant clinical and genetic factors of AIS recurrence, and to investigate the combined effect of genotypes on the occurrence of a second cerebral ischemic attack. METHODS: We investigated a cohort study of AIS patients (18-50 years old) followed in the neurology department over 5 years. Traditional and genetic risk factors were carried through a multivariable logistic regression model. We used a Cox proportional hazard model for identifying predictors of recurrence. RESULTS: Two hundred and seventy patients were enrolled in our study. The risk of AIS recurrence was 36.2% within 5 years. The potential risk of recurrence of AIS increased with traditional and genetic risk factors such as hypertension, diabetes mellitus, heart failure, and family history of cerebrovascular diseases. This risk increased with increasing number of genetic factors. The hazard ratio (HR) was 0.66 (95% confidence interval [CI] 0.97-2.67) for the subject with one genetic factor, 1.61 (95% CI 0.97-2.25) for combined methylenetetrahydrofolate reductase (MTHFR) polymorphisms, and 2.57 (95% CI 1.32-4.99) for combined factor V Leiden (FVL) and MTHFR polymorphisms (677 or 1298). The HR for the three polymorphisms combined was 6.04 (95% CI 2.40-15.16). CONCLUSIONS: Our findings suggest that cumulative effect of both traditional and common genetic risk factors was associated with recurrence of ischemic stroke. We demonstrated for the first time that a combined genotype FVL/MTHFR profile increase the risk of a second cerebral ischemic attack.
BACKGROUND: The involvement of traditional risk factors and combined genetic markers of recurrent arterial ischemic stroke (AIS) in adults remains unclear. OBJECTIVE: This study aims to determine significant clinical and genetic factors of AIS recurrence, and to investigate the combined effect of genotypes on the occurrence of a second cerebral ischemic attack. METHODS: We investigated a cohort study of AIS patients (18-50 years old) followed in the neurology department over 5 years. Traditional and genetic risk factors were carried through a multivariable logistic regression model. We used a Cox proportional hazard model for identifying predictors of recurrence. RESULTS: Two hundred and seventy patients were enrolled in our study. The risk of AIS recurrence was 36.2% within 5 years. The potential risk of recurrence of AIS increased with traditional and genetic risk factors such as hypertension, diabetes mellitus, heart failure, and family history of cerebrovascular diseases. This risk increased with increasing number of genetic factors. The hazard ratio (HR) was 0.66 (95% confidence interval [CI] 0.97-2.67) for the subject with one genetic factor, 1.61 (95% CI 0.97-2.25) for combined methylenetetrahydrofolate reductase (MTHFR) polymorphisms, and 2.57 (95% CI 1.32-4.99) for combined factor V Leiden (FVL) and MTHFR polymorphisms (677 or 1298). The HR for the three polymorphisms combined was 6.04 (95% CI 2.40-15.16). CONCLUSIONS: Our findings suggest that cumulative effect of both traditional and common genetic risk factors was associated with recurrence of ischemic stroke. We demonstrated for the first time that a combined genotype FVL/MTHFR profile increase the risk of a second cerebral ischemic attack.