Functional Inference of Methylenetetrahydrofolate Reductase Gene Polymorphisms on Enzyme Stability as a Potential Risk Factor for Down Syndrome in Croatia

Abstract

Abstract. Understanding the biochemical structure and function of the methylenetetrahydrofolate reductase gene (MTHFR) provides new evidence in elucidating the risk of having a child with Down syndrome (DS) in association with two common MTHFR polymorphisms, C677T and A1298C. The aim of this study was to evaluate the risk for DS according to the presence of MTHFR C677T and A1298C polymorphisms as well as the stability of the enzyme configuration. This study included mothers from Croatia with a liveborn DS child (n = 102) or DS pregnancy (n = 9) and mothers with a healthy child (n = 141). MTHFR C677T and A1298C polymorphisms were assessed by PCR-RFLP. Allele/genotype frequencies differences were determined using χ 2 test. Odds ratio and the 95% confidence intervals were calculated to evaluate the effects of different alleles/genotypes. No statistically significant differences were found between the frequencies of allele/genotype or genotype combinations of the MTHFR C677T and A1298C polymorphisms in the case and the control groups. Additionally, the observed frequencies of the stable (677CC/1298AA, 677CC/1298AC, 677CC/1298CC) and unstable (677CT/1298AA, 677CT/1298AC, 677TT/1298AA) enzyme configurations were not significantly different. We found no evidence to support the possibility that MTHFR polymorphisms and the stability of the enzyme configurations were associated with risk of having a child with DS in Croatian population.

Polymorphisms of the MTHFR gene in mothers of children with trisomy 21 (Down syndrome) in a Polish population

“…This applies equally to studies of Caucasians and of other populations. Worth mentioning, i.a., are studies on French (Chango et al, 2005), 18 Italian (Stuppia et al, 2002), 19 Danish (Kokotas et al, 2009), 20 and Croatian (Vraneković et al, 2010) 21 populations. In addition, analogous studies which also excluded the association of DS with the SNP polymorphisms 677CT and 1298AC were carried out in Jordan (Sadiq et al, 2011), 22 Romania (Bucerzan et al, 2017), 6 Brazil (Balarin et al, 2017), 5 Turkey (Boduroglu et al, 2004), 23 China (Jiajin et al, 2018), 1 and India (Kohli et al, 2008;Kaur et al, 2013;Mohanty et al, 2012).…”

Evaluation of c677t and a1298c polymorphism of the methylenetetrahydrofolate reductase gene as a maternal risk factor for trisomy 21 (a monocentric study)

“…There have also been studies in Brazil (7,12,17) and a few studies in Arab populations, such as in the United Arab Emirates (6), Egypt (13) or Jordan (16). Very few studies have been conducted in Caucasian populations and Europe; only in Italy (8,10,22), Turkey (20,24), and Croatia (24). To date, the Romanian situation has been reported in a single study investigating the polymorphisms of MTHFD gene (MIM *172460) (5).…”

“…Rai et al (2006) reported in Eastern India that the presence of two polymorphisms of the MTHFR gene (MIM *607093) (C677T and A1298C) increased the risk of trisomy 21 to a greater extent than the presence of a single polymorphism (9). Other studies failed to demonstrate correlations between MTHFR gene (MIM *607093) polymorphisms and the risk of trisomy 21 in children (20)(21)(22)(23)(24).…”

Prevalence of methylenetetrahydrofolate reductase 677 C-T polymorphism among mothers of Down syndrome children

“…The results from our study were consistent with various studies. [2678910111213] Several reports have suggested that higher frequency of T allele is associated with risk of non-disjunction. [121415] Meguid et al .…”