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  • The aim of our study was to investigate

    2021-09-17

    The aim of our study was to investigate the polymorphisms of RAGE and glyoxalase I gene and sRAGE serum levels in patients with pathological pregnancy trying to describe the genetic background of pathological pregnancy or to find a new biochemical marker (sRAGE) of these pathological states in pregnancy.
    Subjects and methods
    Results
    Discussion This is the first prospective study dealing with polymorphisms of the RAGE gene (−429 T/C, −374 T/A, Gly82Ser, 2184A/G) and glyoxalase I gene (Glu111Ala) in pregnant women with threatening preterm labor, pregnancy induced hypertensive disorders, ICP and IUGR. No differences in genotype and haplotype frequencies were found among studied groups. Moreover, we did not detect altered sRAGE serum concentrations in patients with IUGR and ICP. Similarly to previous studies we found increased sRAGE serum levels in patients with threatening preterm labor and preeclampsia. The role of RAGE in the pathogenesis of non-pregnancy associated diseases has been already shown. Lately, research focused on physiological and pathological pregnancy, showed the importance of RAGE in human gestation. Cooke et al. studied the expression of RAGE in the myometrium of non-pregnant women, women with physiological pregnancy and patients with preeclampsia and showed expression of RAGE in myometrium of healthy pregnant women and intense expression of RAGE in patients with preeclampsia [20]. The latest study showed no differences in RAGE expression in cervices of patients with preterm or term birth [25]. Yet, only one research aimed on RAGE polymorphisms in patients with pathological pregnancy, especially in patients with gestational diabetes. Santos et al. studied functional polymorphisms of RAGE gene (−429 T/C, −374 T/A) in the promoter region and found that these 2 polymorphisms are not associated with gestational diabetes in Euro-Brazilian population [21]. Our study assessed mentioned functional polymorphisms (−429 T/C, −374 T/A) of RAGE gene promoter, 1 RAGE intron polymorphism (2184A/G) and 1 RAGE valeriana te polymorphism (557 G/A known as Gly82Ser). Genotype frequencies in RAGE and GLO1 gene polymorphisms corresponded to expected frequencies according to HWE in healthy pregnant controls and women with pathological pregnancy. We did not find any differences in genotype nor in haplotype frequencies among studied groups, however groups of patients with preeclampsia, ICP and IUGR were too small to make a statistical conclusion. Our study showed the association of the GA genotype of RAGE Gly82Ser polymorphism with significantly lower sRAGE serum levels in healthy pregnant women. A similar trend was found in women with pathological pregnancy. The association of RAGE Gly82Ser polymorphism with sRAGE serum concentration has valeriana te been already described in several populations [26], [27], [28], however was for the first time described during pregnancy in our study. The RAGE Gly82Ser polymorphism appears to be important. N-linked glycosylation of RAGE is fundamental in the regulation of ligand binding. Two N-glycosylation sites are located in or near the AGE binding domain. Gly82Ser polymorphism is located in the 2nd N-glycosylation motif and increases RAGE affinity to AGEs [29] and influences S100 B proteins binding to RAGE as well [30]. Glyoxalase I, a metalloenzyme, is a part of the glyoxalase system that degrades methylglyoxal, the most common and reactive precursor of AGEs. The role of AGEs in pathological pregnancy, especially in preeclampsia has been shown in several studies [22], [31]. Chekir et al. pointed out an increased concentration of AGEs in placentas of women with preeclampsia. Despite this finding only one study aimed at the role of glyoxalase I in pathologic pregnancy. Sankaralingam et al. showed decreased activity of glyoxalase I in vasculature of women with preeclampsia. Our study is the first to analyze the single nucleotide polymorphism of glyoxalase I gene. We did not show any connection of non‐synonymous A419C (Glu111Ala) polymorphism of glyoxalase I which has impact on glyoxalase I activity [13] with pathological nor physiological pregnancy, even though the role of AGEs and glyoxalase I in preeclampsia has been already confirmed.