Polymorphisms in genes involved in folate metabolism as maternal risk factors for congenital heart diseases of the fеtus

Abstract

Aim of the study was to determine the role of the maternal genotype of the rs1801133 and rs1801131 loci of the MTHFR gene and rs2236225 of the MTHFD1 gene as the risk factor risk of congenital heart defects in offspring. Materials and Methods. The cases group consisted of 42 women who gave the fеtus with congenital defects of the heart and its large vessels. The control group included 85 women who gave birth to healthy children without a complicated genetic and obstetric history. The study used the polymerase chain reaction method, thermostable Taq polymerase oligonucleotide primers and restriction endonuclease (Thermo Fisher Scientific, USA). For the analysis of MTHFR 677C>T MTHFR 1298A>C and MTHFD1 1958G>A polymorphic loci, the RFLP method (restriction fragment length polymorphism) was used. Results and Discussion. According to the results of genetic testing and statistical calculations, the distribution of the genotypes and alleles of the polymorphic loci of MTHFR and MTHFD1 genes were compared with the control group. It was found that in cases group was significantly higher the frequency of the minor T allele of the polymorphic locus 677 C>T of the MTHFR gene (rs1801133) and the frequency of the TT genotype (pT and 1298 A>C of the MTHFR gene and 1958G>A of the MTHFD1 gene in women with congenital heart defects of the fetus were established. It was found that the carrier of the T allele of polymorphic variant 677 C> T of the MTHFR gene in a woman doubles the risk of congenital heart defects of the fetus. Homozygous TT and the heterozygous CT genotype of the polymorphic variant C677T of the MTHFR gene in a woman are genetic factors for increased risk of formation congenital heart defects of offspring. To improve the system of preconception prevention and early diagnostics of the congenital heart defects, effective medical genetic counseling and prognosis of healthy offspring, it is proposed to include the determination of the genotype of the locus 677 C>T gene MTHFR of pregnant women as a risk of congenital heart defects of the fetus and required folic acid supplementation for prevention during the periconception period.

Keywords

• congenital heart defects, birth defects, folate cycle genes