Impact of RFC1, MTHFR, and MTHFD1 polymorphism on unexplained pregnancy loss (UPL): comparative analysis of maternal and fetal components using mother-abortus paired samples.

In this study, we aimed to investigate associations between polymorphisms of folate metabolic pathway genes and unexplained pregnancy loss (UPL) using matched maternal-fetal samples. A total of 113 mother-abortus and 92 mother-newborn samples were collected. Among the 113 mother-abortus samples, 50 with chromosomal abnormality and 22 with maternal cell contamination were excluded. Samples were genotyped for RFC-1 80A>G, MTHFD1 1958 G>A, MTHFR 677C>T, and MTHFR 1298A>C polymorphisms using restriction fragment length polymorphism markers. The genotypes of RFC-1 80A>G, MTHFD1 1958 G>A, MTHFR 677C>T, and MTHFR 1298A>C were not associated with UPL in maternal samples. In the fetal samples, the frequency of heterozygous genotype (GA) of MTHFD11958 G>A was significantly higher than that that of the control (OR = 2.477, 95% CI = 1.128-5.446, p = 0.037). The AA-GA genotypes of MTHFD1 1958G>A and RFC-1 80A>G were significantly higher in mother-abortus samples (p = 0.016) than in the mother-newborn samples (p = 0.029). Frequencies of allelic combinations of MTHFR 677C>T/MTHFD11958G>A and RFC-1 80A>G/MTHFR677C>T/MTHFD1 1958G>A were significantly higher in maternal samples of the UPL group. In the fetal samples, no significant differences were detected between the UPL group and the control group. This study is the first to show associations between MTHFD1 1958G>A, RFC-1 80G>A, MTHFR 677C>T, and MTHFR 1298A>C polymorphisms and UPL and to compare the effects of maternal and fetal samples on UPL using mother-abortus matched samples of Korean origin.