Prediction of Congenital Malformations in The Fetus Based on The Carriage of Single Nucleotide Variants of Folate Cycle Genes by a Mother with Epilepsy

The prediction and prevention of congenital malformations in the fetus of women with epilepsy is an urgent problem due to the need for long-term use of antiepileptic drugs. The aim was to study the frequency of carriage of single-nucleotide variants (SNVs) 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 congenital malformations of the fetus (CMF). Materials and methods. The study included 61 patients with epilepsy who had a history of one or more pregnancies with a known outcome due to the presence of CMF in the child. The patients were divided into two groups: 20 patients had various CMF (the main group), 41 patients had children who were born without CMF (the comparison group). DNA was isolated from the blood, and genotyping of five DNA sequences in four genes was performed by polymerase chain reaction. The frequencies of genotypes and alleles in the mothers of the main group and the comparison group were determined, the differences were assessed using Pearson's chi-square criterion (χ2) and Fisher's exact criterion. Results. There were no statistically significant differences in the frequencies of genotypes and alleles for all analyzed SNVs between the main group and the comparison group (p > 0.05). There were no statistically significant differences in the frequencies of genotypes and alleles of SNVs of the studied genes in mothers of children with CMF (n = 14) and without CMF (n = 22) taking valproic acid (p > 0.05). A statistically significant relationship has been revealed between the carrier of a certain haplogroup of the mother and the formation of CMF. Conclusion. The development of VPD in a child is a multifactorial phenomenon in which genetic factors with a small effect size can play a role only in the case of certain unfavorable combinations.