THE ROLE OF 4a4b POLYMORPHISM OF THE eNOS GENE IN THE DEVELOPMENT OF LETHAL OUTCOMES OF SEVERE INTRAVENTRICULAR HAEMORRHAGE IN PRETERM INFANTS

Artyomova N. S., Kovalova O. M., Pokhylko V. I., Tsvirenko S. M., Zhuk L. A.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

Severe intraventricular haemorrhage in preterm infants are one of the main paediatric public health problems, since mortality in this disease in the last 20 years is not decreasing, and up to 50% of the surviving infants have cognitive and developmental disorders. Taking into account the currently known pathogenetic mechanisms of the disease development, the main of which are inflammation, coagulation disorders and vascular factors, we hypothesized that it is polymorphism in the enzymes encoding the enzyme of eNOS and renin-angiotensin system (AGTR1, ACE), that may affect the development of severe IVH and occurrence of lethal outcomes. The aim of the research is to confirm the hypothesis that the development of severe IVH, as well as lethal outcomes in preterm infants is associated with the polymorphism of the genes eNOS, AGTR1, and ACE. Object and methods. The prospective study was conducted, which included 97 preterm infants (average gestational age 29.07 ± 0.34 weeks; birth weight 1320.8 ± 54.68) who were treated at the medical institutions of Poltava region during 2012-2015. The distribution of I/D genotypes of ACE gene polymorphism, A/C polymorphism of AGTR1 gene and 4a4b polymorphism of eNOS gene among the examined children was studied. Intraventricular haemorrhages were diagnosed according to Papil’s criteria. The material for conducting laboratory studies was blood (0.25 ml) of newborns, which was taken on the first day of life. To determine the polymorphic variants of the ACE, AGT2R1 and eNOS genes, polymerase chain reaction was performed followed by the restriction analysis of amplification reaction products. A simple and multiple logistic regression analysis was used to establish the relationship between the occurrence of severe IVH and lethal outcomes in preterm infants and the effect of clinical and genetic risk factors. Research results. The distribution of polymorphic genotypes of eNOS, AGTR1, ACE genes in infants with and without IVH did not significantly differ. The genetic model of the ID + DD of ACE gene was found in 84.62% of infants without IVH and in 77.59% of infants with severe IVH; the genetic model of AC + CC of ACE gene in 59.26% and 50.0% of infants, and the genetic model ab + bb of eNOS gene in 28.21% and 34.48% of infants, respectively. The study of the distribution of polymorphic genotypes of renin-angiotensin system genes in the examined survivors with severe IVH and those who died showed a lack of significant differences in the frequency of genetic model of ID + DD of ACE gene (83.3% and 73.53%, p = 0.378), the genetic model of AS + SS of AGTR1 gene (37.5% and 58.82%, p = 0.110), and on the verge of statistical significance, the frequency of the genetic model ab + aa of eNOS gene (20.83 + 44.12 p = 0.058). Relevant associations were found between the development of lethal outcomes preterm infants with severe IVH and the genetic model of ab + bb of eNOS gene (OR 6.05 (95% CI 1.08-33.79; p = 0.040) with birth weight (OR 0, 99 (95% CI 0.996-0.999), p = 0.023), gestational age (OR 0.72 (95% CI 0.54-0.96), p = 0.028) and severe RDS (OR 11.3 (95% CI 2.02-63.03), p = 0.006). Conclusion. аb+bb polymorphism of eNOS gene is an independent predictor of the increased risk of developing lethal outcomes in preterm infants with severe IVH.

preterm infants, severe intraventricular haemorrhage, lethal outcomes, polymorphism of genes eNOS, AGTR1, ACE

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«Bulletin of problems biology and medicine» Issue 4 Part 3 (141), 2017 year, 95-100 pages, index UDK 612.6.05-02:616-03688-02:616.831-005.1]-053.32

10.29254/2077–4214–2017–4–3–141–95-100