Relationship between methylenetetrahydrofolate reductase (MTHFR) gene (A1298C) polymorphism with the risk of stroke: A systematic review and meta-analysis

Abstract

Studies on relationship between methylenetetrahydrofolate reductase gene (MTHFR) gene A1298C polymorphism with the risk of ischemic as well as hemorrhagic stroke have shown discordant results. Present meta-analysis was aimed to clarify the relationship between MTHFR gene A1298C polymorphism with risk of stroke. A comprehensive literature search for all published articles was performed in electronic database including PubMed, EMbase, Cochrane Library, Trip Databases, Worldwide Science, CINAHL, and Google Scholar up to 31st December 2019. Pooled odds ratio (ORs) with 95% confidence interval (CIs) under dominant, recessive, and allelic models was calculated. Sensitivity analysis was also performed to detect the heterogeneity. In our meta-analysis, a total of 20 studies with 19 case control studies involving 2871 ischemic stroke (IS) cases and 3984 controls and 3 studies with 201 hemorrhagic stroke cases and 1349 controls were included. Our findings suggest that there was a significant relationship between MTHFR gene A1298C gene polymorphism with risk of ischemic stroke (dominant model: OR = 1.32, 95% CI = 1.06-1.66, recessive model: OR = 1.45, 95% CI = 1.06-1.99 and allelic model: OR = 1.35, 95% CI = 1.00-1.84, respectively). However, no significant relationship between MTHFR gene A1298C gene polymorphism with the risk of hemorrhagic stroke. Findings of this meta-analysis concludes that MTHFR gene A1298 C polymorphism could be capable of increasing stroke susceptibility in Asian, but not in Caucasian population. Genotyping of MTHFR gene A1298C polymorphism may be used as a predictor for the occurrence of ischemic stroke.

Keywords: Methylenetetrahydrofolate reductase; gene polymorphism; hemorrhagic stroke; ischemic stroke; meta-analysis; stroke.