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,Kinga Toboła-Wróbel,Aleksander Jamsheer,Marek Pietryga,Ewa Wysocka,Grażyna Kasprzak

doi:10.3390/jcm11051190

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.

Highlights

Trisomy 21 (T21), Down syndrome, is one of the most common prenatally diagnosed aneuploidies
Since the 1990s, there has been a main diagnostic scheme, implemented between 11 and 13 + 6 weeks of pregnancy, created by Professor Kypros Nicolaides, a world expert in fetal medicine. It consists of the assessment of the concentration of free β-subunit of human chorionic gonadotropin β and pregnancy-associated plasma protein A (PAPP-A) in the mother’s serum, with maternal age and measurement of nuchal translucency (NT) and the heart rate (FHR) in a fetus by ultrasound evaluation, which enable the detection of approximately 80–90% of T21 cases at false-positive rate results (FPR) of about 5% [1,2,3,4]
This study examined whether there are differences in the occurrence of reference and alternative variants of genes of the folate pathway in pregnant women carriers of these variants in whom abnormal values of PAPP-A and free β-hCG multiple of the medians (MoMs) characteristic for T21 were observed

Summary

Introduction

Trisomy 21 (T21), Down syndrome, is one of the most common prenatally diagnosed aneuploidies. Since the 1990s, there has been a main diagnostic scheme, implemented between 11 and 13 + 6 weeks of pregnancy, created by Professor Kypros Nicolaides, a world expert in fetal medicine It consists of the assessment of the concentration of free β-subunit of human chorionic gonadotropin β (free β-hCG) and pregnancy-associated plasma protein A (PAPP-A) in the mother’s serum, with maternal age and measurement of nuchal translucency (NT) and the heart rate (FHR) in a fetus by ultrasound evaluation, which enable the detection of approximately 80–90% of T21 cases at false-positive rate results (FPR) of about 5% [1,2,3,4]. The step in the folate transformation pathway is the conversion of methionine to S-adenosylmethionine (SAM), which is the main contributor of the methyl groups that is involved in the regulation of the functions of nucleic acids, mainly the methylation processes (Figure 1) [5,6,7,8,9,10,11,12,13,14,15,16]

Results

Discussion

Conclusion