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. 2022 Feb 23;11(5):1190.
doi: 10.3390/jcm11051190.

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

Katarzyna Ziółkowska  1   2 , Kinga Toboła-Wróbel  2   3 , Marek Pietryga  2   3 , Grażyna Kasprzak  1 , Aleksander Jamsheer  4   5 , Ewa Wysocka  1
Affiliations

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

Katarzyna Ziółkowska et al. J Clin Med. .

Abstract

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 β-subunit of human chorionic gonadotropin β (free-β-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 β-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 β-hCG MoM values remain independent risk factors for fetal-T21.

Keywords: PAPP-A; folate pathway; free β-hCG; gene polymorphism; trisomy 21.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Simplified overview of the human folate metabolic pathway [10]. Enzymes: CBS: cystathionine b-synthase; GART: phosphoribosyl glycinamide transformylase; MTHFD1: methylenetetrahydrofolate dehydrogenase; MAT: methionine adenosyltransferase; MTHFR: methylenetetrahydrofolate reductase; MTR: methionine synthase; MTRR: methionine synthase reductase; RFC1: reduced folate carrier; TC (TCN2): transcobalamin; TYMS: thymidylate synthase. Metabolites: DHF: dihydrofolate; GSH: glutathione; THF: tetrahydrofolate; dTMP: deoxythymidine monophosphate; dUMP: deoxyuridine monophosphate; SAH: S-adenosyl homocysteine; SAM: S-adenosylmethionine. Cofactors: B12: vitamin B12 or cobalamin.
Figure 2
Figure 2
Frequency of occurrence of reference and alternative alleles of selected variants c.665C>T MTHFR, c.1286A>C MTHFR, c.2756A>G MTR, c.66A>G MTRR and c.776G>C TCN2 in the control group (dark bar) and the study group (light bar).
Figure 3
Figure 3
The frequency of the genotypes (homozygous and heterozygous) of selected variants c.665C>T MTHFR, c.1286A>C MTHFR, c.2756A>G MTR, c.66A>G MTRR and c.776G>C TCN2 in the control group (dark bar) and the study group (light bar).
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