Meta-analysis study to evaluate the association of MTHFR C677T polymorphism with risk of ischemic stroke

Abstract

Ischemic stroke is a condition characterized by reduced blood supply to part of the brain, initiating the ischemic cascade, leading to dysfunction of the brain tissue in that area. It is one of the leading causes of death and disability and is estimated to cause around 5.7 million deaths worldwide. Methyl tetra hydro-folate reductase (MTHFR) is a rate limiting enzyme in the methyl cycle which catalyzes the only biochemical reaction which produces 5, Methyl tetra hydro folate, the co-substrate for the re-methylation of homocystiene to produce methionine. MTFHR C677T is a common mutation of MTHFR and those homozygous for the MTFHR C677T produce a thermo-labile form of the protein with drastically reduced catalytic activity resulting in elevated plasma homocystiene levels - a common risk factor for cardiovascular diseases. However, the role of MTHFR C677T in ischemic stroke remains unclear. To evaluate this association, we carried out a meta-analysis of existing published studies, which included 72 studies involving 12390 cases and 16274 controls. The forest plot was made to evaluate the overall risk of the mutation in the etiology of Ischemic Stroke. The overall Odds- ratio of the study was found to be 1.319 for random effects model, revealing a ∼32% increased risk of Ischemic stroke in the presence of MTHFR C667T mutation compared to controls. Publication bias in the study was analyzed using funnel plot which revealed that only 7 studies out of the 72 contributed to publication bias. These 7 studies were excluded and Meta-analysis was repeated for 65 studies and overall odds-ratio was 1.306, which showed that there was a 30% higher risk of Ischemic stroke in the presence of MTHFR C667T.

Common Variations in Prothrombotic Genes and Susceptibility to Ischemic Stroke in Young Patients: A Case-Control Study in Southeast Iran

“…However, Cui showed the association between this polymorphism and adult IS in Asians and Caucasians, but not in Africans [ 34 ]. Abhinand et al analyzed 72 studies and found that this polymorphism may lead to a 1.3-fold increased risk of IS [ 35 ].…”

Bilateral thalamic stroke in patient with patent foramen ovale and hereditary thrombophilia

“…В одном из мета-анализов показано, что вариант MTHFR 677 C→T ассоциирован с большим риском развития ишемического инсульта в регионах с низких потреблением фолатов (ОШ 1,68; 95% ДИ 1,44-1,97), чем в регионах с высоким уровнем потребления фолатов (ОШ 1,03; 95% ДИ 0,84-1,25). По данным одного из последних мета-анализов, включавшего 72 исследования с 12 390 пациентами с ишемическим инсультом и 16 274 пациентами в группе контроля, наличие генетического полиморфизма C667T повышало риск развития ишемического инсульта на 30% [16].…”

Correlations between plasma homocysteine and MTHFR gene polymorphism and white matter lesions

“…N-5, N-10-methylenetetrahydrofolate reductase (MTHFR) is the rate limiting enzyme in the metabolism of Hcy. Studies have found that MTHFR has a certain correlation with cerebrovascular disease [1,2] and has a predictive value in ischemic stroke [25]. However, the relationship between MTHFR gene C677T polymorphism and WML is still unclear.…”