Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism rather than homocysteine increase the risk of ischemic stroke-associated executive dysfunction

Abstract

Background: An executive dysfunction is a form of cognitive impairment commonly found in ischemic stroke patients with a significant impact on the patients' quality of life. The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and homocysteine ​​are considered important risk factors for stroke and various forms of cognitive dysfunction. This study aimed to investigate the association between the MTHFR C677T polymorphism and serum homocysteine levels and the risk of ischemic stroke-associated executive dysfunction. Method: 87 ischemic stroke patients within the first three months of stroke onset in West Nusa Tenggara General Hospital, Siti Hajar Hospital, and Mataram General Hospital were recruited. Serum homocysteine levels were assessed using ELISA. The MTHFR C677T polymorphism was analyzed using the PCR-RFLP procedure. The executive function of the patients was evaluated using Trail Making Test Part-B, verbal fluency, and backward digit span tests. Results: The mean age of the subjects was 54.1 years. CT scan data revealed that 78.2% of subjects had a small infarct size. The MTHFR C677T polymorphism frequency was 25.3%, consisting of 2.3% homozygous and 23.0% heterozygous mutants. Multivariate logistic regression analysis showed that patients with MTHFR C677T polymorphism were more likely to have executive dysfunction than those with the wild-type genotype of the MTHFR gene (OR 4.53, 95% CI 1.06–19.27, p = 0.041). However, patients with hyperhomocysteinemia (≥13 μmol/l) were not associated with an increased risk of executive dysfunction. Conclusion: The MTHFR C677T polymorphism was the risk factor for ischemic stroke executive dysfunction.