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

Оlena Rechkina; Nataliia Gorovenko; Vira Stryzh; Zoia Rossokha; Svitlana Kyriachenko; Serhii Rudenko

doi:doi:10.11648/j.ajim.20200804.17

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

Оlena Rechkina, Nataliia Gorovenko, Vira Stryzh, Zoia Rossokha, Svitlana Kyriachenko, Serhii Rudenko

Published in American Journal of Internal Medicine (Volume 8, Issue 4)

Received: 14 February 2020 Accepted: 22 April 2020 Published: 4 August 2020

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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.

Published in	American Journal of Internal Medicine (Volume 8, Issue 4) This article belongs to the Special Issue New Approaches to Manage Difficult-to-Control, Severe Asthma
DOI	10.11648/j.ajim.20200804.17
Page(s)	182-191
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2024. Published by Science Publishing Group

Keywords

Bronchial Asthma, Children, Genotype

References

[1]	Global Strategy for Asthma Management and Prevention (2019 update). URL: https://ginasthma.org/wp-content/uploads/2019/06/GINA-2019-main-report-June-2019-wms.pdf.
[2]	Miriam F. Moffatt et al. (2010). A large-scale, consortium-based genomewide association study of asthma. N Engl J Med. 363: 1211–21. doi: 10.1056/NEJMoa0906312.
[3]	Bossé Y., Hudson T. J. (2007). Toward a comprehensive set of asthma susceptibility genes. Annu. Rev. Med. 58: 171–84. doi: 10.1146/annurev.med.58.071105.111738.
[4]	Vercelli D. (2008). Discovering susceptibility genes for asthma and allergy. Nat. Rev. Immunol. 8 (3): 169–82. doi: 10.1038/nri2257.
[5]	Castro M. et. al. (2018). The role of GSTT1 and GSTM1 gene polymorphisms in bronchial asthma. European Respiratory Journal. 52: PA4223. doi: 10.1183/13993003.congress-2018. PA4223.
[6]	Turner S. et. al. (2018). Variants in genes coding for glutathione S-transferases and asthma outcomes in children. Pharmacogenomics. 19 (8): 707–713. doi: 10.2217/pgs-2018-0027.
[7]	Jesenak M., Zelieskova M., Babusikova E. (2017). Oxidative Stress and Bronchial Asthma in Children – Causes or Consequences? Front. Pediatr. 24; 5: 162. doi.org/10.3389/fped.2017.00162.
[8]	Ober C. (2016). Asthma Genetics in the Post-GWAS Era. Ann. Am. Thorac. Soc. Vol 13.1: S85–90. doi: 10.1513/AnnalsATS.201507-459MG.
[9]	Lytvynets L. Y. (2013). Oxidative stress and antioxidant defense in children with varying degrees of bronchial asthma control. Child's health. 8: 71–74.
[10]	Lisitsa A. V. et al. (2010). The dynamics of oxidative stress indicators in patients suffering from exacerbation of bronchial asthma during inhalation therapy with liposomal drugs. Pulmonology. 1: 74–79.
[11]	Wang I. J., Tsai C. H., Chen C. H. (2011). Glutathione S-transferase, incense burning and asthma in children. Eur. Respir. J. Vol. 37(6): 1371–77. doi: 10.1183/09031936.00137210.
[12]	Piacentini S., Polimanti R., Moscatelli B. (2012). Lack of Association Between GSTM1, GSTP1, and GSTT1 Gene Polymorphisms and Asthma in Adult Patients From Rome, Central Italy // J. Investig. Allergol. Clin. Immunol. 22. 4: 252–256.
[13]	C. Hanene С. et al. (2007). Association of GST genes polymorphisms with asthma in Tunisian children. Mediators Inﬂam. 37: 1150–57. doi: 10.1155/2007/19564.
[14]	Mahmoud M. I., Kassem H. S., Nashwa H. (2011). The association between glutathione S-transferase P1 polymorphisms and asthma in Egyptians. Alexandria Journal of Medicine. 47: 105–115. doi: 10.1016/j.ajme.2011.06.008.
[15]	Angeline T., Isabel W., Tsongalis J. (2010). Endothelial nitric oxide gene polymorphisms, nitric oxide production and coronary artery disease risk in a south Indian population. Exp. Mol. Pathol. 89 (3): 205–208. doi: 10.1016/j.yexmp.2010.08.009.
[16]	Crisan D., Carr J. (2000). Angiotensin I-Converting Enzyme. Genotype and Disease Associations. J. Mol. Diagn. 2 (3): 105–115. doi: 10.1016/S1525-1578(10)60624-1.
[17]	Eryuksel E., Ceyhan B. B., Rifat B. (2009). Angiotensin converting enzyme gene polymorphism in Turkish asthmatic patients. Journal of Asthma. 46; 4: 335–338. doi.org/10.1080/02770900802660972.

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Оlena Rechkina, Nataliia Gorovenko, Vira Stryzh, Zoia Rossokha, Svitlana Kyriachenko, et al. (2020). Models of Gen-gene Interaction in Determining the Severity of Bronchial Asthma in Children. American Journal of Internal Medicine, 8(4), 182-191. https://doi.org/10.11648/j.ajim.20200804.17

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ACS Style

Оlena Rechkina; Nataliia Gorovenko; Vira Stryzh; Zoia Rossokha; Svitlana Kyriachenko, et al. Models of Gen-gene Interaction in Determining the Severity of Bronchial Asthma in Children. Am. J. Intern. Med. 2020, 8(4), 182-191. doi: 10.11648/j.ajim.20200804.17

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AMA Style

Оlena Rechkina, Nataliia Gorovenko, Vira Stryzh, Zoia Rossokha, Svitlana Kyriachenko, et al. Models of Gen-gene Interaction in Determining the Severity of Bronchial Asthma in Children. Am J Intern Med. 2020;8(4):182-191. doi: 10.11648/j.ajim.20200804.17

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@article{10.11648/j.ajim.20200804.17,
  author = {Оlena Rechkina and Nataliia Gorovenko and Vira Stryzh and Zoia Rossokha and Svitlana Kyriachenko and Serhii Rudenko},
  title = {Models of Gen-gene Interaction in Determining the Severity of Bronchial Asthma in Children},
  journal = {American Journal of Internal Medicine},
  volume = {8},
  number = {4},
  pages = {182-191},
  doi = {10.11648/j.ajim.20200804.17},
  url = {https://doi.org/10.11648/j.ajim.20200804.17},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajim.20200804.17},
  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.},
 year = {2020}
}

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TY - JOUR
T1 - Models of Gen-gene Interaction in Determining the Severity of Bronchial Asthma in Children
AU - Оlena Rechkina
AU - Nataliia Gorovenko
AU - Vira Stryzh
AU - Zoia Rossokha
AU - Svitlana Kyriachenko
AU - Serhii Rudenko
Y1 - 2020/08/04
PY - 2020
N1 - https://doi.org/10.11648/j.ajim.20200804.17
DO - 10.11648/j.ajim.20200804.17
T2 - American Journal of Internal Medicine
JF - American Journal of Internal Medicine
JO - American Journal of Internal Medicine
SP - 182
EP - 191
PB - Science Publishing Group
SN - 2330-4324
UR - https://doi.org/10.11648/j.ajim.20200804.17
AB - 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.
VL - 8
IS - 4
ER -

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Author Information

Оlena Rechkina

Department of Pediatric Pulmonology and Allergology, National Institute of Phthisiology and Pulmonology, Named After Feophil Gavrilovich Yanovskiy NAMS of Ukraine, Kyiv, Ukraine
Nataliia Gorovenko

Shupyk National Medical Academy of Postgraduate Education, Kyiv, Ukraine
Vira Stryzh

Department of Pediatric Pulmonology and Allergology, National Institute of Phthisiology and Pulmonology, Named After Feophil Gavrilovich Yanovskiy NAMS of Ukraine, Kyiv, Ukraine
Zoia Rossokha

Reference Center for Molecular Diagnostics of the Ministry of Health of Ukraine, Kyiv, Ukraine
Svitlana Kyriachenko

Reference Center for Molecular Diagnostics of the Ministry of Health of Ukraine, Kyiv, Ukraine
Serhii Rudenko

Department of Pediatric Pulmonology and Allergology, National Institute of Phthisiology and Pulmonology, Named After Feophil Gavrilovich Yanovskiy NAMS of Ukraine, Kyiv, Ukraine

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APA Style

Оlena Rechkina, Nataliia Gorovenko, Vira Stryzh, Zoia Rossokha, Svitlana Kyriachenko, et al. (2020). Models of Gen-gene Interaction in Determining the Severity of Bronchial Asthma in Children. American Journal of Internal Medicine, 8(4), 182-191. https://doi.org/10.11648/j.ajim.20200804.17

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ACS Style

Оlena Rechkina; Nataliia Gorovenko; Vira Stryzh; Zoia Rossokha; Svitlana Kyriachenko, et al. Models of Gen-gene Interaction in Determining the Severity of Bronchial Asthma in Children. Am. J. Intern. Med. 2020, 8(4), 182-191. doi: 10.11648/j.ajim.20200804.17

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AMA Style

Оlena Rechkina, Nataliia Gorovenko, Vira Stryzh, Zoia Rossokha, Svitlana Kyriachenko, et al. Models of Gen-gene Interaction in Determining the Severity of Bronchial Asthma in Children. Am J Intern Med. 2020;8(4):182-191. doi: 10.11648/j.ajim.20200804.17

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@article{10.11648/j.ajim.20200804.17,
  author = {Оlena Rechkina and Nataliia Gorovenko and Vira Stryzh and Zoia Rossokha and Svitlana Kyriachenko and Serhii Rudenko},
  title = {Models of Gen-gene Interaction in Determining the Severity of Bronchial Asthma in Children},
  journal = {American Journal of Internal Medicine},
  volume = {8},
  number = {4},
  pages = {182-191},
  doi = {10.11648/j.ajim.20200804.17},
  url = {https://doi.org/10.11648/j.ajim.20200804.17},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ajim.20200804.17},
  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.},
 year = {2020}
}

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