Mthfr C677t, Hyperhomocysteinemia, and Their Interactions with Traditional Risk Factors in Early Neurological Deterioration In Chinese Patients with Ischemic Stroke

OBJECTIVE: This study aimed to evaluate the relationship between the methylenetetrahydrofolate reductase (MTHFR) gene and the risk of early neurological deterioration (END) in patients with ischemic stroke (IS) in a Han Chinese population. METHODS: Patients with acute IS in Chengdu (Sichuan, China) were recruited between January 2017 and June 2019. A candidate gene association study design, using a single nucleotide polymorphism as the genetic marker, was used to analyze the association between MTHFR and END risk. Furthermore, gene–environment interaction analyses were performed to obtain insights into risk factors for END. RESULTS: In this study, 434 subjects with acute IS were enrolled, and 129 cases of END (29.7%) were detected during the study period. Hyperglycemia, neurological function impairment on admission, and hyperhomocysteinemia were all associated with END in the first week after admission. The C677T polymorphism of MTHFR was also significantly associated with END risk (TT genotype: odds ratio [OR] = 1.710, 95% confidence interval [CI] = 1.021–2.863, P = 0.043; T allele: OR = 1.58, 95% CI = 1.181–2.121, P = 0.002). Furthermore, interactions among MTHFR C677T, drinking, high blood glucose on admission, and National Institutes of Health Stroke Scale scores > 5 increased susceptibility to END (OR = 1.237); however, this result was not significant (P = 0.806). CONCLUSIONS: MTHFR was associated with END risk in a Han Chinese population in Chengdu. Gene–environmental risk factor interactions may be important for the pathophysiology of END.