An Assessment of Selected Molecular and Biochemical Markers of the Folate Pathway as Potential Risk Factors for Fetal Trisomy 21 during the First Trimester of Pregnancy in the Polish Population

Are the maternal gene variants MTHFR: c.665C > T, MTHFR: c.1286A > C, MTR: c.2756A > G, MTRR: c.66A > G, RFC1: c.80C > T and TCN2: c.776G > C and blood markers of the folate pathway important factors in assessing the risk of fetal trisomy 21 (fetal-T21)? Twenty pregnant women with a high risk and twenty with a low risk of fetal-T21 underwent prenatal examination. Selected gene variants and folate pathway markers and pregnancy-associated plasma protein A (PAPP-A) and free beta-subunit of human chorionic gonadotropin beta (free-beta-hCG) multiple of the medians (MoMs) were determined. The distributions of the alternative alleles and genotypes of the gene variants did not differ between the studied groups. There was no relationship between PAPP-A and beta-hCG MoM values and the presence of allele alternative genotype variants. The occurrence of alternative variants of the selected genes and concentrations of most of the studied folate pathway markers may not play a crucial role in the risk of fetal-T21 in pregnant women. However, the relationships between erythrocyte folate concentrations and the occurrence of alternative variants: c.665C > T MTHFR and c.776G > C TCN2, as well as the methylmalonic acid concentration and the occurrence of alternative variant c.776G > C TCN2 in pregnant women with fetal-T21, encourage further research. So far, of the biochemical markers, maternal PAPP-A and beta-hCG MoM values remain independent risk factors for fetal-T21.

Automated summary

This study investigated the role of maternal gene variants and blood markers of the folate pathway in assessing the risk of fetal trisomy 21. The results suggest that the selected gene variants and most of the studied folate pathway markers may not play a crucial role in the risk of fetal trisomy 21. However, further research is needed to explore the relationship between certain gene variants and folate concentrations in pregnant women with fetal trisomy 21.