The TT genotype of methylenetetrahydrofolate reductase 677C>T polymorphism increases the susceptibility to pediatric ischemic stroke: meta-analysis of the 822 cases and 1,552 controls

Abstract

The 677C>T polymorphism within methylenetetrahydrofolate reductase (MTHFR) gene is related to an elevated level of homocysteine. Thus it may be considered as a genetic risk factor in ischemic stroke. Apparently studies of this type of polymorphism in childhood stroke have shown conflicting results. We performed meta-analysis of all the data that are available in relation with MTHFR polymorphism and the risk of ischemic stroke in children. We searched PubMed (last search dated December 2010) using “MTHFR polymorphism”, “ischemic stroke” “child”, “children”, “pediatric stroke” as keywords and reference lists of studies and reviews on the topic. Finally, 15 case–control studies corresponded to the inclusion criteria for meta-analysis. These studies involved the total number of 822 children and adolescents after ischemic stroke and 1,552 control subjects. Fixed or random effects models were used depending on the heterogeneity between the studies. The association between ischemic stroke and 677C>T polymorphism within MTHFR gene was observed in three of the studies. The pooled analysis showed that TT genotype of MTHFR gene is more common in stroke patients than in controls (p = 0.0402, odds ratio = 1.57, 95 % confidence interval 1.02–2.41). The Egger’s test did not reveal presence of a publication bias. The results based on a sizeable group of cases and controls have proved that the 677C>T polymorphism in MTHFR gene is associated with the development of ischemic stroke in children.

Association of C677T polymorphism in the methylenetetrahydrofolate reductase gene (MTHFR gene) with ischemic stroke: a meta-analysis

“…20 A meta-analysis of 14 studies, conducted by SareckaHujar et al showed that TT genotype of MTHFR gene was more common in pediatric stroke patient than controls (OR 1.57, 95% CI 1.02-2.41). 21 Another meta-analysis, which included 19 case-control studies involving 2223 cases and 2936 controls also suggested that MTHFR C677T polymorphism was significantly associated with increased risk of ischemic stroke. 14 The mechanism of association between MTHFR polymorphism and ischemic stroke is not clear; however, studies have shown that a single base pair replacement of Cytosine nucleotide with Thymine at 677 nucleotide position of MTHFR gene influences enzyme thermolability, its decreased activity and, in turn, the elevated level of Hcy, an endothelial toxin especially in the presence of low folate levels 22 and in effect to elevated risk of stroke.…”

Is the 1298A>C polymorphism in the MTHFR gene a risk factor for arterial ischaemic stroke in children? The results of meta-analysis

“…A previous meta-analysis of available data [11] confirmed the association between the carrier state of the 677T allele in the MTHFR gene and AIS in children. However, the role of another common MTHFR polymorphism, 1298A>C in paediatric stroke, is still uncertain.…”

Risk Factors for Recurrent Arterial Ischemic Stroke in Children and Young Adults

“…In turn, in children with AIS from Lebanon, 677C>T polymorphism within the MTHFR gene was found to be present in the patients who suffered from recurrent stroke, as well as those who had multiple risk factors for AIS [67]. Previously, the T allele carrier-state of 677C>T polymorphism in the MTHFR gene was proved to increase the risk of AIS in children [68], in contrast to another common 1298A>C polymorphism in the MTHFR gene [69]. The polymorphic 677TT variant of the MTHFR gene was previously linked to a higher level of homocysteine, one of the biochemical risk factors for cerebroand cardiovascular diseases, both in children and adults.…”