Abstract

BackgroundHyperhomocysteinemia (HHCY) is a risk factor for cardiovascular and cerebrovascular diseases. The C677T 5, 10-methylenetetrahydrofolate reductase (MTHFR) gene polymorphism increases homocysteine (HCY) levels. This study analyzed the relationship between C677T MTHFR polymorphism and the therapeutic effect of lowering HCY in stroke patients with HHCY.MethodsBaseline data were collected from stroke patients with HHCY for this prospective cohort study. The C677T MTHFR genotype was detected by polymerase chain reaction-restriction fragment length polymorphism and the therapeutic effect to reduce HCY was compared.ResultsOf 200 stroke patients 162 (81.0%) completed follow-up and were evaluated. Most of them responded well to treatment (103 cases, 63.5%), but 59 (36.4%) patients were in the poor efficacy group. There was a significant difference in terms of age (P < 0.001), hypertension (P = 0.041), hyperuricemia (P = 0.042), HCY after treatment (P < 0.001), and MTHFR genotype (P < 0.001) between the poor efficacy and effective groups, with increased frequency of the TT genotype in the poor efficacy group. Logistic regression showed that the T allele was associated with poor efficacy (OR = 0.733, 95%CI: 0.693, 0.862, P < 0.001). In the codominant model the TT genotype was associated with poor outcome (OR = 0.862, 95%CI: 0.767, 0.970, P = 0.017) and this was also the case in the recessive model (OR = 0.585, 95%CI: 0.462, 0.741, P < 0.001) but there was no association between CT and TT in the dominant model.ConclusionsThe T allele and TT genotype of the MTHFR C677T polymorphism was associated with poor HCY reduction treatment efficacy in stroke patients with HHCY.Trial registrationThe registration number of the clinical trial is ChiCTR1800020048. Registration date: December 12, 2018.

Highlights

  • Hyperhomocysteinemia (HHCY) is a risk factor for cardiovascular and cerebrovascular diseases

  • Patients with an abnormally high level of HCY, or hyperhomocysteinemia (HHCY), are considered to be at risk of cardiovascular and cerebrovascular diseases [10,11,12], but its mechanism is rather complex, and not fully understood. 60.6% of stroke patients have HHCY, which is associated with a low level of serum B12 [13]

  • This study aimed to compare the relationship among C677T methylenetetrahydrofolate reductase (MTHFR) gene polymorphism and the risk of stroke, and the therapeutic effect of lowering HCY in stroke patients with HHCY

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Summary

Introduction

Hyperhomocysteinemia (HHCY) is a risk factor for cardiovascular and cerebrovascular diseases. The traditional risk factors of stroke, such as hypertension, diabetes mellitus, hyperlipidemia, and atrial fibrillation have been studied extensively, and their underlying mechanisms for stroke are evident [2]. This has led to primary prevention measures that have been implemented to decrease the incidence of stroke in high income countries [1]. Patients with an abnormally high level of HCY, or hyperhomocysteinemia (HHCY), are considered to be at risk of cardiovascular and cerebrovascular diseases [10,11,12], but its mechanism is rather complex, and not fully understood. It has been suggested that differences between studies are related to the heterogeneity of cerebral infarction [25,26,27]

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