Abstract
INTRODUCTION: the relationship between elevated plasma homocysteine (Hcy) and stroke has been established, but this association remains indistinct in cryptogenic stroke in adults. Our aim is to investigate the association between homocysteine, vitamins B9 and B12, and cryptogenic stroke. Furthermore, to determine the correlation between methylenetetrahydrofolate reductase (MTHFR) polymorphism and biochemical levels in plasma. METHODS: we conducted a retrospective case-control study including 100 cryptogenic stroke patients aged 18-50 years and 100 participants with age-and-sex-matched healthy controls. Clinical, radiological, and outcome data from cerebral venous thrombosis (CVT) patients were recorded. Homocysteine, vitamin B9, and vitamin B12 were analyzed. Deoxyribonucleic acids (DNAs) from both groups were tested. MTHFR C677T mutation was assessed by restriction fragment length polymorphism (PCR). All analyses were performed using Statistical Package for the Social Sciences (SPSSV.20) software. Multivariable logistic regression analysis was performed to identify factors associated with stroke risk and clinical outcomes. RESULTS: a total of 200 cases were included in this study, 50% (n=100) patients with cryptogenic stroke (mean age of 40.49 ± 6.2 years, sex-ratio= 1.5) and 50% (n=100) healthy cases (mean age of 39.09 ± 5.8 years, sex-ratio= 1.5). The elevated plasma level of Hcy and vitamin B9 levels deficiency increase the risk of cryptogenic stroke occurrence (aOR: 2.5; 95% (0.71-5.25), P=0.01), (aOR: 3.1; 95% (1.6-9.6), p=0.02 respectively). Additionally, vitamin B9 deficiency was significantly associated with elevated Hcy levels (4.57 ± 3.59; p=0.001). Genetic analysis revealed a significant association between homozygous TT genotype of the MTHFR C677T polymorphism, elevated Hcy levels (20.4 ± 7.07; p=0.001) and vitamin B9 deficiency (4.9±3.9; p=0.001). Furthermore, the combined CT/AC genotype was associated with elevated Hcy level (21.6 ± 9.6; p=0.001) and vitamin B9 deficiency (2.9 ± 1.0; p=0.04). CONCLUSION: the presence of homozygote MTHFR C677T or dual heterozygous MTHFR C66T and A1298C, which leads to elevated Hcy and deficiency of vitamin B9 plasma levels, is correlated with an increased risk of cryptogenic stroke occurrence among adult Tunisian patients.