Methylenetetrahydrofolate Reductase Gene Polymorphism and Childhood Stroke

Morita, Denise C.; Donaldson, Amy; Butterfield, Russell J.; Benedict, Susan; Bale, James F.

doi:10.1016/j.pediatrneurol.2009.04.017

Cited by 22 publications

(15 citation statements)

References 11 publications

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“…Two studies contained case groups of both ischemic and hemorrhagic strokes, and 11 studies contained case groups of ischemic strokes only. In all studies, except two where such information was missing (Akar et al, 2001;Morita et al, 2009), genomic DNA was extracted from blood samples. Genotyping was performed consistently across studies with polymerase chain reaction (PCR).…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Several independent studies have investigated the role of the MTHFR A1298C polymorphism in stroke risk (Table 1) (Akar et al, 2001;Linnebank et al, 2005;Sun et al, 2005;Komitopoulou et al, 2006;Sazci et al, 2006;Nan et al, 2007;Sirachainan et al, 2008;Biswas et al, 2009;Morita et al, 2009;Sawula et al, 2009;Chen et al, 2010;Han et al, 2010;Hultdin et al, 2011), but the results are inconclusive, partially because of the possible small effect of the polymorphism on stroke risk and the relatively small sample size in each of the published studies. To estimate the overall risk of the A1298C polymorphism for strokes, as well as to quantify the potential between-study heterogeneity, we performed a meta-analysis on all eligible published case-control studies.…”

Section: Introductionmentioning

confidence: 99%

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Association of the methylenetetrahydrofolate reductase gene A1298C polymorphism with stroke risk based on a meta-analysis

Lu²,

Wu³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. Several independent studies have reported the role of the methylenetetrahydrofolate reductase gene (MTHFR) A1298C polymorphism in strokes, but the results are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed in the present study. In this meta-analysis, a total of 13 studies, including 1974 cases and 2660 controls, were selected to evaluate the possible association. Crude odds ratios (ORs) with 95% confidence intervals (CI) were used to assess the strength of the association in additive, dominant, and recessive models. The overall analysis showed that MTHFR A1298C polymorphism and strokes MTHFR A1298C was associated with a significant increase in the risk of stroke in the heterozygote comparison (AC vs AA: OR = 1.17; 95%CI = 1.03-1.34) and in the dominant model (AC/CC vs AA: OR = 1.22; 95%CI = 1.01-1.49). Stratified analysis showed a significantly strong association between the MTHFR A1298C polymorphism and stroke risk in Asian populations (OR = 1.32 for AC vs AA; OR = 1.94 for CC vs AA; OR = 1.37 for AC/CC vs AA; OR = 1.33 for C vs A allele), but not in Caucasian populations. Additionally, the MTHFR 1298C allele was found to be a risk factor for developing ischemic strokes. However, no statistically significant increased risk of hemorrhagic stroke was found in any of the genetic models. In conclusion, this meta-analysis supported that the MTHFR A1298C polymorphism could be capable of increasing stroke susceptibility in Asian, but not in Caucasian, populations.

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Section: Study Characteristicsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of the methylenetetrahydrofolate reductase gene A1298C polymorphism with stroke risk based on a meta-analysis

Lu²,

Wu³

et al. 2013

Genet. Mol. Res.

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“…1. Finally, eight case-control studies were included in the meta-analysis with a total number of 426 paediatric patients with AIS and 778 control subjects [12][13][14][20][21][22][23][24].…”

Section: Methodsmentioning

confidence: 99%

“…In order to genotype the MTHFR 1298A>C polymorphism, PCR-RFLP analysis was used in four of the studies [12,13,20,21], CVD StripAssays in two studies [14,22] and Taqman PCR in one study [23]. The genotyping method was not specified in one of the studies [24]. The largest groups of AIS patients were recruited by Balcerzyk et al [12], Herak et al [14] and Komitopoulou et al [22], whereas the fewest patients were recruited by Gelfand et al [23] and Morita et al [24].…”

Section: Study Characteristicsmentioning

confidence: 99%

“…The genotyping method was not specified in one of the studies [24]. The largest groups of AIS patients were recruited by Balcerzyk et al [12], Herak et al [14] and Komitopoulou et al [22], whereas the fewest patients were recruited by Gelfand et al [23] and Morita et al [24]. The largest group of control subjects was analysed in the study by Sirachainan et al [21] and the lowest one in the study by Biswas et al [13].…”

Section: Study Characteristicsmentioning

confidence: 99%

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

2018

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An elevated level of homocysteine is a risk factor for vascular diseases, brain atrophy and several other disorders. The 1298A>C polymorphism (rs1801131) leads to mildly decreased MTHFR activity. Previously, it was observed that the MTHFR 1298A>C polymorphism in combined analysis with the MTHFR 677C>T polymorphism increases homocysteine levels. However, conflicting results on its relation to ischaemic stroke in children can be found. We conducted a meta-analysis to analyse possible connections between the MTHFR 1298A>C polymorphism and ischaemic stroke in paediatric patients. We identified available data published before December 2016 using appropriate keywords and searching PubMed as well as the references cited in the found articles. Eight case-control studies were included in the meta-analysis (426 children with stroke and 778 controls). Statistical analyses were made using R and Comprehensive Meta-Analysis softwares to investigate the impact of polymorphism in four models: dominant, recessive, additive and allelic. No publication bias was observed in the meta-analysis. We demonstrated no relationship between the 1298A>C polymorphism and ischaemic stroke in children in the case of recessive, additive and allelic models. However, the results of the dominant model analysis should be treated with caution due to the sensitivity analysis results. After omitting one of the included study, we observed a significant association between the carriers of the MTHFR C allele (cases with AC + CC genotypes) and ischaemic stroke in children (OR 1.35 95% CI 1.02-1.79, p = 0.035 in a fixed effects model). In conclusion, the 1298A>C polymorphism in the MTHFR gene is not a risk factor for ischaemic stroke in paediatric patients.

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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

et al. 2012

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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.

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Methylenetetrahydrofolate Reductase Gene Polymorphism and Childhood Stroke

Cited by 22 publications

References 11 publications

Association of the methylenetetrahydrofolate reductase gene A1298C polymorphism with stroke risk based on a meta-analysis

Association of the methylenetetrahydrofolate reductase gene A1298C polymorphism with stroke risk based on a meta-analysis

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

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

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