Polymorphism 677C→T MTHFR Gene in Mexican Mothers of Children With Complex Congenital Heart Disease

Abstract

Congenital heart defects (CHD) are the third leading cause of death in children <1 year of age in Mexico where there is a high prevalence of the 677C → T polymorphism of the MTHFR gene. This is important because the homozygous 677T/T MTHFR gene and deficiency of folic acid (FA) intake have been associated with CHD. Our objective was to analyze the possible association between the genotype 677T/T of the MTHFR gene and supplementation of FA in Mexican women with the presence of complex CHD in their children. We analyzed genotypes of 31 mothers of children with complex CHD (group I) and 62 mothers of healthy children (group II) and investigated FA supplementation during pregnancy in both study groups. Allele frequencies in group I were 41.9 % for C and 58.1 % for T and 22.6 % for genotype frequencies CC, 38.7 % for CT, and 38.7 % for TT. Allele frequencies in group II were 63.7 % for C and 36.3 % for T and 38.7 % for genotype frequencies CC, 50 % for CT and 11.3 % for TT. Both populations are in Hardy-Weinberg equilibrium. Odds ratio for having a child with a complex CHD was 5.9, p = 0.008 (95 % CI 1.67; 20.63) for the TT genotype. FA supplementation at any time during pregnancy was 90.3 and 87.9 % in groups II and I respectively (p > 0.05). Association was found between the maternal genotype (677/TT MTHFR) with the presence of complex CHD in their offspring. No differences in FA supplementation during any stage were found between groups.

A Meta-Analysis of the Relationship Between Maternal Folic Acid Supplementation and the Risk of Congenital Heart Defects

“…According to the search strategy, a total of 20 citations were included in the meta-analysis. 4,14,15,19,[24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39] The characteristics and information of the eligible studies are shown in Supplemental Table I. Nine articles were written in English and 11 in Chinese.…”

“…Previous studies have revealed that maternal MTHFR 677C→T polymorphism (rs1801133) is associated with the risk of CHDs and the carriers with MTHFR 667TT genotype had a higher risk of CHDs in their offspring. 25,26,32,[42][43][44] Furthermore, Li, et al indicated that MTHFR 667TT genotype had a synergistic effect with a deficiency of FA intake for CHD occurrence. 25) Thus, an early diagnosis of MTHFR 677C→T polymorphism in pregnant women or before conception would assist in planning optimal and timely treatment, thus decreasing neonatal and infant mortality attributed to CHDs.…”

The Association of the MTHFR c.1625A>C Genetic Variant with the Risk of Congenital Heart Diseases in the Chinese

“…However, the exact etiology of CHD still remains poorly understood. Recently, several studies have indicated that the methylenetetrahydrofolate reductase (MTHFR) gene is an important candidate gene for influencing the prognosis of patients and the risk of CHD (Chambers et al, 2000;Junker et al, 2001;Klerk et al, 2002;Lee et al, 2005;Pereira et al, 2005;Hobbs et al, 2006;Zhu et al, 2006;van Beynum et al, 2007;Brandalize et al, 2009;Garcia-Fragoso et al, 2010;Nie et al, 2011;Gong et al, 2012;Sanchez-Urbina et al, 2012;Yin et al, 2012;Balderrabano-Saucedo et al, 2013;Mamasoula et al, 2013;Mehlig et al, 2013;Wang et al, 2013;Zidan et al, 2013;Wang et al, 2014;Zhang et al, 2014). MTHFR genetic variants, such as C677T and A1298C, have been reported and identified with respect to their genetic influences on the risk of CHD in different populations (Chambers et al, 2000;Junker et al, 2001;Klerk et al, 2002;Nie et al, 2011;Wang et al, 2013;Zidan et al, 2013).…”

The methylenetetrahydrofolate reductase C677T polymorphism and the risk of congenital heart diseases: a literature review

“…MTHFr catalyzes the biologically irreversible reduction of dietary folate, 5,10-methylenetetrahydrofolate, into 5-methylenete-© C I C E d i z i o n i I n t e r n a z i o n a l i trahydrofolate, the predominant circulatory form of folate and the methyl donor for the vitamin B12 -dependent remethylation of homocyseine to methionine (3,32,33,36). Methionine is ultimately converted to s-adenosylmethionine, which acts as a methyl donor for dnA, rnA, proteins and phospholipids methylation (34). In addition, methylenetetrahydrofolate participates in dnA synthesis by converting uracil to thyamine (34).…”

“…Methionine is ultimately converted to s-adenosylmethionine, which acts as a methyl donor for dnA, rnA, proteins and phospholipids methylation (34). In addition, methylenetetrahydrofolate participates in dnA synthesis by converting uracil to thyamine (34). A common missense mutation, more precisely a cytosine (C) to thymine (T) substitution at base 677 that cause a replacement of valine for alanine at position 222 of the protein, produces a thermolabile variant of MTHFr with reduced enzymatic action resulting in higher plasma levels of homocysteine, especially in individuals with low-folate levels (37,38).…”