The Role of Genotype Combinations of Various Genes in Predicting the Risk of Fetal Congenital Anomalies

Abstract

Significance. Congenital fetal anomalies are one of the pressing issues in modern medicine, as they account for a significant proportion of perinatal morbidity and mortality. The development of congenital malformations is determined by a complex interaction of genetic and environmental factors. Genes involved in the metabolism of folates, homocysteine, and the biotransformation of xenobiotics play a particularly important role in the pathogenesis of embryonic development disorders.
Objective of the study. To investigate the role of polymorphic variants of the MTR A>G, MTRR A>G, and CYP1A2 C>T genes, as well as to assess their contribution to the risk of fetal congenital anomalies.
Materials and Methods. A study was conducted involving 95 women, of whom 55 constituted the main group (pregnant women with fetal developmental abnormalities) and 40 constituted the control group. We analyzed the distribution of genotypes and alleles of the polymorphic variants of the MTR, MTRR, and CYP1A2 genes, calculating the odds ratio (OR), 95% confidence interval (95% CI), χ² statistics, and various inheritance models.
Results. A statistically significant association was established between polymorphic variants of the studied genes and the risk of fetal congenital anomalies. For the MTR A>G gene, the presence of the G allele was associated with an increased risk of pathology (OR = 17.7; 95% CI: 5.28–59.8; p = 0.0001). For the MTRR A>G polymorphism, the strongest association was identified: the G allele increased the risk of fetal abnormalities (OR = 80.17; 95% CI: 18.73–343.03; p = 0.0001). The CYP1A2 C>T polymorphism was also characterized by a significant association with fetal pathology (OR = 25.67; 95% CI: 7.63–86.46; p < 0.0001). Analysis of inheritance models revealed a statistically significant association under additive, multiplicative, and dominant models.
Conclusion. The results indicate that polymorphic variants of the MTR, MTRR, and CYP1A2 genes can be considered potential genetic markers of an increased risk of fetal congenital anomalies. A comprehensive assessment of genotype combinations of various genes holds promise for the development of models for individualized genetic risk prediction of pregnancy complications.