The role of single nucleotide variants of folate cycle genes of a mother with epilepsy in the occurrence of congenital malformations of the fetus

Abstract

Aim - To study the frequency of single-nucleotide variants (ONV) rs1801133 and rs1801131 of the MTHFR gene; rs1801394 of the MTRR gene, rs1805087 of the MTR gene and rs1051266 of the SLC19A1 gene in women with epilepsy and to evaluate their associations with major congenital malformations (MCM) of the fetus. Material and methods. The study included 61 women with epilepsy who have children: 20 had different fetal MCM (main group), 41 patients had children born without MCM (comparison group). DNA was extracted from blood, and the genotyping of five ONV into four genes was analyzed by polymerase chain reaction. The frequencies of genotypes and alleles in the mothers of the main and the comparison group were determined, the differences were assessed using Pearson's chi-squared criterion (χ2) and Fisher's exact criterion. Results. There were no statistically significant differences in the frequencies of genotypes and alleles for all analyzed ONV between the main group and the comparison group. There were no statistically significant differences in the frequencies of genotypes and alleles of ONV genes of the folate cycle in mothers of children with malformations (n = 14) and without malformations (n = 22), taking valproic acid. A statistically significant relationship was revealed between the carrier of a certain haplogroup of the mother and the formation of fetal MCM. Conclusion. The MCM in a child is a multifactorial phenomenon in which genetic factors with a small effect size can play a significant role only in the case of certain unfavorable combinations.