<i>MTHFR</i> C677T and A1298C polymorphisms as a risk factor for congenital heart defects in Down syndrome

Božović, Ivana Babić; Vraneković, Jadranka; Čizmarević, Nada Starčević; Mahulja-Stamenković, Vesna; Prpić, Igor; Brajenović-Milić, Bojana

doi:10.1111/j.1442-200x.2010.03310.x

Cited by 28 publications

(30 citation statements)

References 36 publications

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“…[27] Data on the genotype and allele frequencies of MTHFR C677T polymorphism in DS mothers compared to non-DS mothers are numerous and show significant differences, but reports regarding distribution of MTHFR mutant allele and genotype frequencies in DS individuals are very few. [192930313233] Several clinical and experimental studies have hypothesized/reported that patients with DS have disturbed one-carbon metabolism. [23] t-Hcy, vitamin B-12 and folate are metabonutritional factors directly related to this metabolism.…”

Section: Resultsmentioning

confidence: 99%

Methylenetetrahydrofolate reductase polymorphism is not risk factor for Down syndrome in North India

Rai¹,

Yadav²,

Kumar³

et al. 2014

Indian J Hum Genet

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BACKGROUND:Down syndrome (DS) is the most common cause of mental retardation of genetic etiology with the prevalence rate of 1/700 to 1/1000 live births worldwide. Several polymorphisms in folate/homocysteine metabolism pathways genes have been reported as a risk factor in women for bearing DS child, but very few studies investigated these polymorphisms in DS cases whether there are a risk factor for being DS or not.OBJECTIVE:We have investigated the association of methylenetetrahydrofolate reductase (MTHFR) with the occurrence of DS in Indian population. MTHFR is one of the key regulatory enzymes involved in the metabolic pathway of homocysteine responsible for the reduction of methyltetrahydrofolate. A total of 32 DS cases and 64 age, sex matched controls were genotyped for MTHFR C677T polymorphism by polymerase chain reaction-restriction fragment length polymorphism.RESULTS:The observed genotype frequencies were CC = 0.81; CT = 0.17 and TT = 0.02 in controls and CC = 0.81 and CT = 0.19 in DS cases. Frequency of T allele in DS and controls were 0.09 and 0.1, respectively. Significant difference in the distribution of mutant 677T allele was not observed between DS cases and controls (odds ratio = 0.915; 95% confidence intervals: 0.331-2.53; P = 0.864).CONCLUSION:Results of this study indicate that MTHFR C677T polymorphism is not risk factor for DS.

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Section: Resultsmentioning

confidence: 99%

Methylenetetrahydrofolate reductase polymorphism is not risk factor for Down syndrome in North India

Rai¹,

Yadav²,

Kumar³

et al. 2014

Indian J Hum Genet

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“…Also the functional MTHFR c.1298A polymorphism was over-transmitted to cases with atrioventricular septal defects (P = 0.05) and under-transmitted to controls (P = 0.02) 8 . By contrast, others have failed to observe the association of maternal MTHFR polymorphisms with CHDs in the DS offspring 27 . The study population included 112 DS subjects and CHDs were present in 48% of the DS subjects.…”

Section: Maternal Folate Metabolism and Risk Of Congenital Heart Defementioning

confidence: 94%

“…The study population included 112 DS subjects and CHDs were present in 48% of the DS subjects. The mothers of 107 DS individuals were available for the study and none were peri-conceptional folic acid users 27 . However, despite some conflicting results, the vast majority of recent studies suggest that lack of folic acid supplementation at peri-conception coupled with genetic variants of the folate metabolic pathway might represent maternal risk factors for CHDs in the DS child (Table 3).…”

Section: Maternal Folate Metabolism and Risk Of Congenital Heart Defementioning

confidence: 99%

Advances in the genetic aspects linking folate metabolism to the maternal risk of birth of a child with Down syndrome

Copped¹

2013

OA Genetics

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Introduction In 1999, it was first hypothesised that maternal polymorphisms of genes involved in folate metabolism might represent maternal risk factors for the birth of a child with Down syndrome. Several research articles have been produced worldwide to address that question, and recent meta-analyses of the literature suggest that at least two polymorphisms, namely MTHFR c.677C>T and MTRR c.66A>G, are associated with increased maternal risk for trisomy 21. Moreover, there is indication for an additive contribution of variants in folate pathway genes to the maternal risk for having a birth with Down syndrome. In addition, lack of folate supplementation at periconception combined with genetic polymorphisms of folate pathway genes, might represent maternal risk factors for congenital heart defects in the child with Down syndrome. The aim of this critical review was to discuss advances in genetic aspects linking folate metabolism to the maternal risk of giving birth to a child with Down syndrome. Conclusion Despite encouraging results, several factors such as ethnicity, age, dietary habits, and many others, could modulate those interactions and we are still far away from a complete understanding of the relationship between folate metabolism and chromosome 21 non-disjunction.

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“…Results about DS and MTHFRC677T polymorphism as a risk factor of its occurrence are still conflicting. The recent meta-analysis suggested that MTHFR 677T is a major risk factor for DS birth [105], while previous smaller studies did not recognize such risk [106,107]. Studies performed analyzing peripheral lymphocytes of women with DS offspring revealed several markers of global genome instability, including an increased frequency of micronuclei, shorter telomeres, and impaired DNA methylation at MTHFR promoter [108,109].…”

Section: Epigenetic Genetic and Nutrigenomic Risk Factors For Congementioning

confidence: 99%

Global DNA Methylation as a Potential Underlying Mechanism of Congenital Disease Development

Stanković¹

2020

DNA Methylation Mechanism

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During the last decade, quantitative measurement of the methylation status in white blood cells (WBCs) has been used as a potential biomarker in a variety of diseases. Long interspersed nucleotide element-1 (LINE-1) has been used widely as a surrogate marker of global DNA methylation. Altered maternal DNA methylation is suggested to be an underlying mechanism in the trisomy 21 and the development of birth defects, including congenital heart defects (CHDs). The molecular mechanisms that underlie the epigenetic regulation of gene transcription are independent of DNA sequence, but they do depend on environmental stimuli, which are especially important in fetal development in utero environment. Folic acid deficiency and genetic variations of folate pathway genes, such as the methylenetetrahydrofolate reductase gene (MTHFR), are foremost among these maternal risk factors. Also, there are exogenous risk factors (cigarette smoking, alcohol intake, medication use, periconceptional maternal supplementation, body mass index, and dietary habits) with impact on maternal LINE-1 methylation. MTHFR C677T genotype/ diet and other environmental factors as significant predictors of LINE-1 DNA methylation in regard to congenital diseases will be discussed in the chapter.

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MTHFR C677T and A1298C polymorphisms as a risk factor for congenital heart defects in Down syndrome

Abstract: Because the fetus is lost in a great proportion of trisomy 21 pregnancies, both maternal and fetal, not only live-born MTHFR C677T and A1298C, as well as maternal nutrition and lifestyle during pregnancy, should be analyzed to asses the impact on CHD in DS.

Cited by 28 publications

References 36 publications

Methylenetetrahydrofolate reductase polymorphism is not risk factor for Down syndrome in North India

Methylenetetrahydrofolate reductase polymorphism is not risk factor for Down syndrome in North India

Advances in the genetic aspects linking folate metabolism to the maternal risk of birth of a child with Down syndrome

Global DNA Methylation as a Potential Underlying Mechanism of Congenital Disease Development

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