THE INFLUENCE OF GENES OF RENIN-ANGIOTENSIN SYSTEM ON THE DEVELOPMENT OF ASPHYXIA AND ITS COURSE IN TERM INFANTS

Korobka O. V.

CLINICAL AND EXPERIMENTAL MEDICINE

Scentific article

Relevance of the research. Genes of renin-angiotensin system — ACE, AGTR1 and eNOS are biologically and clinically significant in formation of phenotypic course features of most diseases of the perinatal period. The aim of the research. To analyze the impact of I/D polymorphism of ACE gene, A/C polymorphism of AGTR1 gene and 4a/b polymorphism of eNOS gene on the development of asphyxia and its course in term newborns. Materials and methods. A prospective cohort study which included full-term newborns (n = 107) with the gestational age of 37 weeks, birth weight of 2500 g who were treated in intensive care baby unit (ICBU) at medical institutions of Poltava region during 2010-2014 with diagnosis of moderate or severe asphyxia. The comparison group included 31 healthy newborn. Results of the research. The study found that research groups were almost identical in terms of birth weight, the ratio of girls and boys. ID genotype of ACE gene was found in 44.7% of healthy children and in 57.41% of infants with asphyxia, while DD variant of ACE gene — in 15.8% and 25.0% of children respectively. The ratio of possibility to have asphyxia in patients with genotype II was 0.28 (95% CI 0.11-0.72), p = 0.005. The study showed that frequencies of different genotypes options of AGTR1 gene in children of examined groups displayed no significant differences in the distribution of healthy children and neonates with asphyxia according to AA, AC and CC genotypes. Results of the study showed the presence of polymorphic variant 4aa of eNOS gene in 1 infant (3.23%) of the comparison group and 4 infants (3.8%) from the main group, 4ba variant of gene eNOS — in 6 (19.35%) and 31 (29.5%) infants respectively, and 4bb variant of gene — in 24 healthy infants (77.42%) and in 70 (66.7%) infants with asphyxia. We conducted the study of combination of frequency in polymorphic variants of genes of renin-angiotensin system in children with asphyxia and healthy newborns. The presence of the combination of ID or DD genotype of ACE gene with AC or CC genotype of AGTR1 gene is not associated with the development of asphyxia in term infants. We have not received significant differences in the frequency of detection of the combination of polymorphic variants of ACE and eNOS gene, as well as AGTR1 and eNOS genes in infants with asphyxia and children of the comparison group. Among the examined children with asphyxia 38 (35.8%) had severe course, therefore the influence of polymorphic variants of genes of renin-angiotensin system on the severity of asphyxia was analyzed. The ratio of the possibility to have severe asphyxia in a child with II genotype of ACE gene was 0.34, p = 0.037, and the children with DD genotype — 2.77, p = 0.05. Thus, II genotype of ACE gene significantly reduces the chances of the child to have asphyxia and its severe course, and DD genotype conversely increases the chances of a child to have a severe course of asphyxia. II genotype was detected in 39.5% of healthy children and 15.74% of children with asphyxia (PR 0.29, 95% CI 0.11-0.72), p = 0.005), and its severe course in 18.4% (7 of 38) children with asphyxia (PR 0.34, 95% CI 0.103-1.09, p = 0.037). A/C polymorphism of AGTR1 gene and 4b/a polymorphism of eNOS gene are not associated with the development of asphyxia and its severe course. Conclusion. There are no associations between CC genotype of AGTR1 gene and the development of asphyxia (1.722 (95% CI 0.750-3.953, p = 0.200) and its severity (0.345, 95% CI 0.043-2.781, p = 0.317) in full-term infants, as well as between asphyxia and 4aa genotype of eNOS gene (1.19 (95% CI 0.13-11.1, p = 0.680) and 4b/a genotype (1.74, 95% CI 0.65-4.65, p = 0.188) in term infants. There was also no significant effect of combination of polymorphic variants of ACE, AGTR1 and eNOS genes in term infants to develop asphyxia and its severity. II genotype of ACE gene reduces the chances of the child and the mother to develop asphyxia and its severe course in term newborns. Further researches on larger cohort of patients to determine the final role of ACE, AGTR1 and eNOS genes in the development of asphyxia and its severity are needed.

4a/b polymorphism of eNOS gene, I/D polymorphism of ACE gene, A/C polymorphism of AGTR1 gene, asphyxia, full-term newborns

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