Association of glutathion-S-transferase genes (GSTM1, GSTT1, GSTP1) polymorphisms with risk factors for bronchopulmonary dysplasia in prematurely born infants

Abstract

In recent years, there has been an increase in bronchopulmonary dysplasia morbidity in premature infants, which is associated with improved survival. We analyzed the risk factors for bronchopulmonary dysplasia. It is known that the most important factors are low gestational age and birth weight, as well as prolonged use of mechanical ventilation and late onset of neonatal infection. Genetic factors can alter the body’s ability to withstand oxidative stress and infection. Many candidate genes may participate in the development of bronchopulmonary dysplasia, especially those related to the regulation of the growth of alveoli, the inflammatory response, antioxidant protection and recovery processes of cells. For this study we selected glutathione-S-transferase family genes ‒ GSTM1, GSTT1, GSTP1. We carried out a retrospective study on the basis of a case-control. The study included 21 prematurely born babies with bronchopulmonary dysplasia (main group) and 52 premature infants who did not have bronchopulmonary dysplasia (control group). All the children underwent clinical, instrumental and laboratory examination, as well as genetic testing. Polymorphism of the genes in question and various combinations of polymorphic variants do not affect the risk of bronchopulmonary dysplasia and its severity. We have detected the effect of genetic polymorphisms on the indicators that characterize respiratory support, frequency of the use of mechanical ventilation, noninvasive ventilation, oxygen therapy, the duration of mechanical ventilation, the duration of non-invasive ventilation, maximum inspiratory pressure and the risk of bronchopulmonary dysplasia in the infants under study. We have found a similar indirect effect of genetic polymorphisms on other independent risk factor ‒ late neonatal infections. For proper evaluation of the contribution of genetic polymorphism it is necessary to conduct a preliminary analysis of possible clinical and laboratory parameters to identify strong independent predictors, and then analyze the indirect effects of genetic factors. Further research and development of new approaches to the mechanical lung ventilation regimens in premature infants and consideration of the genetic polymorphisms will create a set of preventive measures and reduce the incidence of bronchopulmonary dysplasia.