GENETICALLY SPECIFIED DISORDERS OF FOLATE METABOLISM IN NEONATES WITH CRITICAL CONDITIONS

Abstract

The paper deals with the influence of genetic polymorphisms on the features of folate metabolism and antioxidant protection in newborns with critical conditions in neonatal period. The objective of the study was to examine changes in folate metabolism, antioxidant defense indicators and their relationship with genetic polymorphism to determine the contribution of genetically determined folate metabolism disorders in the development of critical conditions in newborns. To perform the work 45 infants were examined (gestational age 38-40 weeks) with critical conditions of the early neonatal period (the main group) and 30 infants (gestational age 38-40 weeks) with physiological early neonatal period (the comparison group). Examined children were in obstetric and neonatal intensive care units of the Regional Maternity Hospital in Poltava. There were significant differences in the indices of homocysteine, folate and serum glutathione transferase activity in newborns of the examined groups during the first three days of life, with varying strength correlation found. Dynamics of the indices of folate metabolism on the third day of life as compared to the first day was significantly different in the newborns from the main groups and correlated with the indices of antioxidant protection. The peculiarities of the dynamics of folate metabolism indices, characterizing antioxidant and folate dependent metabolic processes in the perinatal period, were determined. The analysis of the intergenic interaction impact on the development of folate metabolism disorders and critical conditions revealed association with polymorphisms of GSTT1, GSTM1, MTHFR, ACE, TNF-a, AT2R1 genes. Synergistic interaction between polymorphic variants of genes GSTT1 and GSTM1, MTHFR and ACE was found. Polymorphic variants of these genes associated with changes in the dynamics of folate metabolism indicators. In the course of the study the best predictive model of intergenic interaction in the development of critical conditions and genetically determined folate metabolism disorders in newborns was found (predictive value - 91.47%). Analysis of unfavorable polymorphic variants in GSTT1, GSTM1, MTHFR, ACE, TNF-a, AT2R1 genes is a perspective one to predict unfavourable early neonatal period in newborns in clinical practice.