Models of Gen-gene Interaction in Determining the Severity of Bronchial Asthma in Children

Abstract

Bronchial asthma (BA) has a polygenic nature, and the onset of its manifestation and features course is realized due to the influence of genetic factors. This study aimed to investigate the effect of polymorphisms of the genes of the phase II detoxification system and genes of the cardiovascular tone on the severity of asthma in children. The study included 163 children aged 5-18 years: 38 with severe asthma, 69 with moderate asthma, and 56 with mild asthma. A molecular genetic study was conducted to determine the frequency of gene propagation and gen-gene interaction by GSTT1, GSTM1, GSTP1, ACE, eNOS, AT2R1, NAT2 genes at different severity of bronchial asthma. Found that in the prediction of the severity of asthma special place belongs to the analysis of the combination of genotypes. Independent effects were found for AT2R1 and ACE gene polymorphisms. The ACE (I / D) / AT2R1 (A1166C) / eNOS (T786C) / eNOS (4b / 4a) four-locus model was developed to predict the severe BA course and the need for additional analysis of the interaction of AT2R1 (A1166C) and eNOS (T786C), eNOS (T786C) genes was demonstrated (4b4a) and GSTT1. The risk of developing severe BA has been demonstrated for the combination of 1166SS + 786TT, 1166CC + 786TC genotypes by AT2R1 (A1166C) and eNOS (T786C) genes, and the reduction of this risk for combinations of eNOS (4b4a) 4b4b + GSTT1 genotypes. In moderate asthma, combinations of ACE genotypes DD + AT2R1 1166SS and AT2R1 313AA + GSTP1 1166SS were reliable risk markers for severe asthma. AT2R1 gene polymorphism was the leading marker in more severe asthma. A marker of severe BA was also found for the heterozygous 857GA polymorphism of the NAT2 gene (G857A). Conclusions. The influence of ACE (I / D), AT2R1 (A1166C), eNOS (T-786C), NAT2 (G857A), GSTT1, and GSTP1 gene polymorphisms on the severity of asthma in children has been established.

Bronchial Asthma: Genetic Factors Contributing to its Pathogenesis

“…The authors point out that individuals carrying ACE D/D genotype predominate (54.2%) among BA patients. This is also supported by a study indicating that children with the D/D genotype are in the group of high risk for BA development [38].…”

Genetically high angiotensin-converting enzyme concentrations causally increase asthma risk: A meta-analysis using Mendelian randomization

“…There is evidence that ACE expressed in the lungs plays a key role in the pathogenesis of bronchial asthma. It is because ACE can mediate the proliferation of smooth vascular muscle cells ( 31 ), which affects aggregation and adhesion of platelets and monocytes and consequently leads to excessive bronchiectasis ( 32 ). The biological mechanism behind the causal implication of circulating ACE in asthma is not clear at present ( 33 ).…”