BACKGROUND

The impact of the methylenetetrahydrofolate reductase () mutation on the relationship between plasma homocysteine (Hcy) levels and stroke has been extensively studied and documented in previous study. However, it remains unclear whether the mutation can affect the response to Hcy lowering treatment in stroke patients with hyperhomocysteinemia (HHcy). Understanding the impact of genetic factors on treatment response can help optimize personalized treatment strategies for stroke patients with HHcy. We aimed to investigate the potential association between the gene polymorphisms and the effectiveness of Hcy lowering treatment using vitamin therapy in stroke patients with HHcy.

METHODS

The genotype polymorphisms were identified using polymerase chain reaction-restriction fragment length polymorphism, and the distribution of three genotypes in the gene locus was compared. The treatment effects of Hcy lowering agents were compared among patients with different genotypes.

RESULTS

Among the 320 stroke patients enrolled in the study, 258 (80.6%) were diagnosed with HHcy. Of these, 162 patients (Effective Group) responded well to the clinical Hcy lowering treatment, while 96 patients (Invalid Group) failed to achieve sufficient response even after taking combination supplements of folic acid, Vitamin B6, and methylcobalamin for one month. Significant differences were observed in terms of age ( < 0.001), hypertension ( = 0.034), dyslipidemia ( = 0.022), hyperuricemia ( = 0.013) and genotype distribution of gene polymorphism ( < 0.001) between the Invalid group and the Effective group. The multivariate regression analysis revealed that the allele (odd rations [OR], 1.327; 95% confidence interval [CI], 1.114-1.580; = 0.0015) was independently associated with an insufficient Hcy lowering treatment effect. Additionally, the genotype was independently associated with insufficient response in both the codominant model (OR, 1.645; 95% CI, 1.093-2.476; = 0.017) and the recessive model ( versus + ; OR, 1.529; 95% CI, 1.145-2.042; = 0.004). However, no relationship was observed between + genotypes and poor treatment effect in the dominate model.

CONCLUSIONS

Our findings suggested that the genotype and T allele of polymorphism were independently associated with an insufficient Hcy lowering treatment effect in stroke patients with HHcy.