Relationship of Methylenetetrahydrofolate Reductase (MTHFR) C677T Variation With Susceptibility of Patients With Ischemic Stroke: A Meta-Analysis

Abstract

Discovery and validation of genetic factors for multifactorial and polygenic disorders like stroke are needed to make progress in precision medicine. Although some traditional risk factors for stroke have been identified, they do not fully explain the pathophysiological mechanism of ischemic stroke. The research of genetic risk factors is becoming increasingly relevant in the understanding of stroke mechanisms and the finding of population-specific therapeutic targets. The methylenetetrahydrofolate reductase (MTHFR) gene is involved in homocysteine metabolism, and a high homocysteine level is a risk factor for stroke. Using a meta-analysis technique, we investigated the link between the MTHFR C677T gene polymorphism and the risk of ischemic stroke. We used the electronic databases PubMed, Medline, Embase, and Google Scholar to find articles in the Journal of Stroke. If heterogeneity was more than 50%, pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random-effects model; otherwise, a fixed-effects model was used. A total of 67 case-control studies with 17,704 cases and 21,981 controls met our inclusion criteria. The Asian population was represented by 41 studies, whereas the Caucasian population was represented by 26. Under the recessive model, a gene polymorphism at the 677 location of the MTHFR gene is related to an elevated risk of ischemic stroke (OR: 1.29, 95% CI: 1.22-1.37, P < 0.001). People who have the MTHFR C677T gene polymorphism have a greater risk of stroke than people who do not.

Associations of MTHFR gene polymorphism with lipid metabolism and risk of cerebral infarction in the Northwest Han Chinese population

“…The TT genotype is commonly linked with elevated Hcy levels through reduction in the activity of MTHFR (23). In the present study, Hcy level was significantly correlated with genotype (CT/TT) of the MTHFR C677T gene polymorphism among both the control and the CI groups, which was consistent with findings in Asian, Singaporean, Malaysian, Tunisian, Chinese, and Polish populations (24)(25)(26)(27)(28). However, studies of Indonesian, Zambian, and Brazilian populations have found no association between MTHFR C677T polymorphism and risk of CI (29-31).…”

Association study between genetic polymorphisms in MTHFR and stroke susceptibility in Egyptian population: a case–control study

“…Mutations in the MTHFR gene, which is involved in homocysteine metabolism, cause increased homocysteine (hcy) buildup in the circulation. As a result, a change in the function of the MTHFR pathway increases the risk of cerebrovascular illness 15 – 17 . To develop precision healthcare, genetic factors for complex and polygenic disorders like stroke must be identified and verified.…”

Homocysteine, Vitamin B12 and Folate Level: Possible Risk Factors in the Progression of Chronic Heart and Kidney Disorders

“…The two main methods for lowering serum Hcy levels are oral FA or 5-MTHF administration or intramuscular injections of FA. However, it should be emphasized that vitamins B12 and B6 are also essential cofactors in the process of metabolizing hydroxy citric acid, in addition to folate [ 46 , 47 ]. One of the two irreversible mechanisms-transsulfuration to cysteine or remethylation to methionine-can easily degrade Hcy because it can be found close to the center of metabolic processes (Fig.…”