CLINICAL AND GENETIC DETERMINANTS OF PERINATAL PATHOLOGY IN NEWBORNS

One of the pressing issues of healthcare nowadays is applying methods of molecular genetics aimed at identifying and assessing genetic risk factors and early diagnosis of perinatal pathology. Numerous studies have contributed to identifying risk factors that affect the health of newborns. The aim of this work is to investigate the associations between the development of perinatal pathology in premature and full-term infants with polymorphism of genes of the glutathione transferase family (GSTT1, GSTM1, GSTP1), renin-angiotensin system (ACE, AGT2R1). Materials and methods. The study included 110 full-term infants with asphyxia, 30 healthy full-term infants for the control group, and 125 preterm infants with perinatal infections, 21 preterm infants with broncho-pulmonary dysplasia, and 70 conditionally healthy preterm infants. A set of routine clinical and laboratory methods of research and determining gene polymorphism was performed. Results. The presence of a non-functional allele of the GSTT1 gene and DD variant of the ACE gene in newborns is associated with the development of severe perinatal asphyxia (p = 0.006 and p = 0.003, respectively). Children with GSTT1 "-" and AC AG2TR1 genotypes have significantly higher levels of diastolic pressure in the first day after birth than children with functional genotypes of these genes (p <0.05). The median mean duration of mechanical ventilation and CPAP in children with GSTT1 genotype "-" was significantly higher than that in children with GSTT1 genotype "+" (p = 0.01 and p = 0.001, respectively). Conclusion. Polymorphism studies of glutathione transferase and renin-angiotensin genes can be used to predict the severity of a child's condition after birth.

Prenatal Exposure to Parabens Affects Birth Outcomes through Maternal Glutathione S-Transferase (GST) Polymorphisms: From the Mothers and Kids Environmental Health (MAKE) Study

Introduction: Human exposure to parabens is very common in daily life, and prenatal exposure to these chemicals is associated with poor birth outcomes. Therefore, the aim of this study was to investigate the effect of glutathione S-transferase (GST) polymorphisms on the association between prenatal exposure to parabens and birth outcomes. Methods: We conducted a multivariate analysis involving 177 subjects to determine the association between paraben concentrations and birth outcomes in mothers with GST mu 1 (GSTM1) and GST theta 1 (GSTT1) polymorphisms from 2017 to 2019. Furthermore, we determined the interactive effect between paraben levels and GSTM1/GSTT1 polymorphisms using regression analysis, in addition to a generalized linear model after stratifying GSTM1/GSTT1 genotype into three categories. Results: Methyl and propyl paraben concentrations were significantly and positively associated with birth weight (methyl, β = 116.525, 95% confidence interval (CI) = 22.460–210.590; propyl, β = 82.352, 95% CI = 9.147–155.557) in individuals with the GSTM1-null genotype. Moreover, the propyl paraben concentration was significantly associated with an increase in gestational age (β = 0.312, 95% CI = 0.085–0.539) in individuals with the GSTM1-null genotype. Conclusions: This study reported the association between prenatal paraben exposure and birth outcomes in individuals with GST polymorphisms. We found positive relationships of maternal exposure to methyl parabens with birth weight in both mothers with GSTM1 and GSTT1-null genotypes.

Modulatory role of GSTM1 null genotype on the frequency of micronuclei in pesticide-exposed agricultural workers

In this study, we aimed to investigate the extent of genotoxic risk and the association between null GSTM1/GSTT1 and GSTP1 Ile105Val variants and cellular DNA damage, as measured by micronucleus (MN) assay in a group of agricultural workers from Denizli, Turkey. Peripheral blood samples were collected from 116 subjects, including 58 workers who were occupationally exposed to pesticides and 58 healthy unexposed controls. The MN frequencies of each individual were assessed by cytokinesis-blocked micronuclei assays on lymphocytes. Genotypes for different GST variants were determined using polymerase chain reaction-based methods. A significant 3.4-fold increase in MN frequency was observed in workers compared with the controls ( p < 0.001). Among the GST genotypes, only the GSTM1 null genotype was found to be significantly associated with an increased MN frequency in workers ( p = 0.01). Individuals with a concomitant null GSTM1/GSTT1 genotype demonstrated a significant ( p = 0.01) increase in MN frequency compared with those with functional isozymes in the exposed worker group. The association of the GSTM1 null genotype with higher MN frequency suggests that it may be a modifier of genotoxic risk in individuals exposed to pesticides and may thus be a candidate susceptibility biomarker for human biomonitoring studies.