Relationship between polymorphism in NOS3, AGTR1, TLR9, DRD4 genes and severity of congenital pneumonia in newborns


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Abstract

Objective. To identify variable region gene polymorphisms associated with the severity of congenital pneumonia in newborns. Material and Methods. The study comprised 101 newborns with confirmed congenital pneumonia requiring respiratory support after birth. The infants were divided into three groups. Group I (n = 63) included newborns whose respiratory therapy was limited to nasal non-invasive support including CPAP or non-invasive mechanical ventilation in the bi-level CPAP (Biphasic) mode. Newborns in group II (n = 25) required endotracheal intubation and invasive ventilation. Group III (n = 13) included newborns requiring aggressive invasive ventilation (МАР > 12 Н2,O и FiO2 > 0.5) and high-frequency oscillatory ventilation (HFOV). All patients were genotyped to identify DNA polymorphism is specific loci. Results. We identified a statistically significant association between the polymorphic locus of the NOS3 gene: -786(р = 0.028), the AGTR1 polymorphic locus: 1166A>C (p = 0.009), the TLR9 polymorphic locus: 1486T>C (р = 0.022) of the DRD4 polymorphic locus: 521C>T (р = 0.04) and severity of the disease, need for aggressive invasive ventilation, and high-frequency oscillatory ventilation (HFOV). Conclusions. Severity of congenital pneumonia in newborns requiring aggressive invasive ventilation (MAP> 12H2O and FiO> 0.5) and HFOV was associated with polymorphism in NOS3 genes (synthesis of endogenous nitric oxide), AGTR1 (angiotensin converting receptor enzyme), TLR9 (toll-like receptor 9 is a membrane protein from the group of toll-like receptors playing an essential role in the innate immunity), and DRD4 (encodes a subtype of D4 receptor dopamine). Model experiments investigating targeted proteins and interaction pathways of the altered gene products are needed to confirm the predictive value and clinical significance of the studied polymorphism.

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About the authors

Oleg V. Ionov

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of Minzdrav of Russia; I.M. Sechenov First Moscow State Medical University of Minzdrav of Russia (Sechenov University)

Email: o_ionov@oparina4.ru
PhD, head of the A.G. Antonov Neonatal Intensive Care Unit, Institute of Neonatology and Pediatrics

Andrey E. Donnikov

V.I. Kulakov NMRC for OG&P of Minzdrav of Russia

Email: a_donnikov@oparina4.ru
PhD, head of the Molecular Genetics Diagnostic Laboratory, Clinical Pathologist

Maria B. Bezlepkina

V.I. Kulakov NMRC for OG&P of Minzdrav of Russia

Email: masha.bezlepkina@mail.ru
MD, anesthesiologist at the A.G. Antonov Neonatal Intensive Care Unit, Institute of Neonatology and Pediatrics

Irina V. Nikitina

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of Minzdrav of Russia

Email: i_nikitina@oparina4.ru
PhD, leading researcher at the Neonatal Intensive Care Unit №2, Institute of Neonatology and Pediatrics, Associate Professor at the Department of Neonatology

Ekaterina N. Balashova

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of Minzdrav of Russia

Email: e_balashova@oparina4.ru
PhD, clinical care supervisor at the A.G. Antonov Neonatal Intensive Care Unit, Institute of Neonatology and Pediatrics, Associate Professor at the Department of Neonatology, Faculty of Pediatrics

Anna R. Kirtbaya

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of Minzdrav of Russia; I.M. Sechenov First Moscow State Medical University of Minzdrav of Russia (Sechenov University)

Email: a_kirtbaya@oparina4.ru
PhD, clinical care supervisor at the A.G. Antonov Neonatal Intensive Care Unit, Institute of Neonatology and Pediatrics

Daria S. Kryuchko

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of Minzdrav of Russia; National Medical Research Center for Children's Health of Minzdrav of Russia

Email: kryuchko.DS@nczd.ru
MD, deputy director for Science of National Medical Research Center for Children’s Health of Minzdrav of Russia. Professor at the Department of Neonatology

Elena N. Baibarina

V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of Minzdrav of Russia

Email: baibarina@oparina4.ru
MD, professor, chief researcher at the Neonatal Intensive Care Unit, Institute of Neonatology and Pediatrics

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