The role of «proteolysis-antiproteolysis» system genes in occupational COPD development.

Authors

  • A. V. Basanets
  • T. A. Ostapenko
  • N. V. Zhurakhivska

DOI:

https://doi.org/10.26641/2307-0404.2018.3(part1).142327

Keywords:

chronic obstructive pulmonary disease (COPD), genetic predisposition, polymorphism

Abstract

COPD is multifactorial disease, in which hereditary predisposition and environmental factors (including work conditions) play an important role. Among the genes associated with possible predisposition to COPD development a group of genes with the expression impacting the activity of “proteolysis-antiproteolysis – MMP2, MM9, TIMP2, A2M, ELN is considered. The main group of 72 underground coal miners with COPD (mean age 53,7±5,8 years, mean work experience – 21,8±4,8 years), and control group of 79 healthy miners (mean age – 48,2±5,6 years, mean work experience – 20,2±4,5 years) were examined. Polymorphism of genes with out bronchopulmonary pathology MMP9, α2M was revealed using PCR with electroforetic detection in agarosegel. Polymorphism of genes TIMP2, MMP2, ELN was revealed using PCR with fluorescent detection (RealTime PCR). By the data of molecular-genetic research among miners with COPD of occupational etiology (main group) and miners without it (control group) there was estabkished a reliable difference for the genotypes:

MMP9*СС,TIMP2*GG;
MMP9*СС,MMP2*CC,TIMP2*G/G,α2M*IIe/IIe,ELN*Gly/Gly; MMP9*СС,MMP2*CТ,TIMP2*G/G,α2M*IIe/Val,ELN*Gly/Gly; MMP9*СС,MMP2*CС,TIMP2*G/G,α2M*IIe/Val,ELN*Ser/Se; MMP9*СТ,MMP2*CC,TIMP2*G/G,α2M*IIe/IIe,ELN*Gly/Ser.
These genotypes are associated with resistance for COPD development in underground coal miners ofUkraine. The obtained results testify to the participation of genes encoding protein synthesis of the system "proteolysantiproteolysis": MMP2, MMP9, TIMP2, A2M, ELN in the formation of genetic predisposition and resistance to the development of COPD of professional etiology in miners, which reveals new opportunities in the prevention of this disease in workers subject to the high concentrations of coal-rock dust.

Author Biographies

A. V. Basanets

SI “Kundiiev Yu.I. Institute for occupational health of the National academy
of medical sciences of Ukraine»
Saksahanskoho str., 75, Kyiv, 01033, Ukraine

T. A. Ostapenko

SI “Kundiiev Yu.I. Institute for occupational health of the National academy
of medical sciences of Ukraine»
Saksahanskoho str., 75, Kyiv, 01033, Ukraine

N. V. Zhurakhivska

SI “Kundiiev Yu.I. Institute for occupational health of the National academy
of medical sciences of Ukraine»
Saksahanskoho str., 75, Kyiv, 01033, Ukraine

References

Basanets AV, Dolіnchuk LV [Role of α2M gene polymorphism in occupational COPD development in ukrainian coal miners]. Medicnі perspektivi. 2017;3:22-28. Ukrainian.

Basanets AV, Ostapenko TA, Dolіnchuk LV [Ro­le of ELN gene polymorphism in occupational COPD de­velopment in ukrainian coal miners]. Ukrainsky pulmo­nologіchny Journal.2017;3:25-28. Ukrainian.

Dolinchuk LV, Basanets AV, Andrushchen­ko TA, Ostapenko TA. [Functional state of the broncho­pulmonary system in coal miners with chronic obstructive pulmonary disease]. The electronic conference "Modern preventive medicine: from medicine to pathology to medicine of health". Moskva. 2013;24-32. Russian.

GarciaFerrer I, Marrero A, GomisRüth FX, Goulas T. α2Macroglobulins: Structure and Function. Subcell Biochem. 2017;83:149-83.

Keene JD, Jacobson S, Kechris K, Kinney GL et. al. Biomarkers predictive of exacerbations in the spi­romics and COPD Gene Cohorts. Am J Respir Crit Care Med. 2017;195(4):473-81.

Bakke PS et al. Candidate genes for COPD in two large data sets. Epub, 2011;37(2):255-63.

Global strategy for asthma management and pre­vention (GINA 2017). Available from: http:// www.ginasthma.org/pdf/GINA_Report_2017.pgf.

Graul Neumann LM, Hausser I, Essayie M, Rauch A et. al. Highly variable cutis laxa resulting from a dominant splicing mutation of the elastin gene. Am J Med Genet A. 2008;146A(8):977-83.

Houghton AM. Matrix metalloproteinases in de­structive lung disease. Matrix Biol. 2015;44-46:167-74.

Wendel DP, Taylor DG, Albertine KH et. al. Im­paired distal airway development in mice lacking elastin. Am J Respir Cell Mol Biol. 2000;23(3):320-6.

Matheson MC, Ellis JA, Raven J, Walters EH et. al. Association of IL8, CXCR2 and TNFalpha polymor­phisms and airway disease. Hum Genet. 2006;51(3):196-203.

Murphy G. Tissue inhibitors of metallopro­tei­nases. Genome Biol. 2011;12(11):233.

Navratilova Z, Kolek V, Petrek M. Matrix Metal­loproteinases and Their Inhibitors in Chronic Obstructive Pulmonary Disease. Arch Immunol Ther Exp (Warsz). 2016;64(3):177-93.

Górka K, Soja J, Jakieła B, Plutecka H et. al. Re­la­tionship between the thickness of bronchial wall layers, emphysema score, and markers of remodeling in bron­cho­alveolar lavage fluid in patients with chronic obs­tructive pul­monary disease. Pol Arch Med Wewn. 2016;126(6):402-10.

Santo Tomas LH. Emphysema and chronic ob­structive pulmonary disease in coal miners. Curr Opin Pulm Med, 2011;17(2):123-5.

How to Cite

1.
Basanets AV, Ostapenko TA, Zhurakhivska NV. The role of «proteolysis-antiproteolysis» system genes in occupational COPD development. Med. perspekt. [Internet]. 2018Oct.26 [cited 2024Nov.19];23(3(part1):11-7. Available from: https://journals.uran.ua/index.php/2307-0404/article/view/142327

Issue

Section

THEORETICAL MEDICINE