Polymorphism rs652438 of gene <i>mmp12</i> and oxidative DNA damage in bronchial asthma: An experimental non-randomised study

Abstract

Background. Personalised medicine is an avenue to create technologies for individual prognosis of the disease onset and development. The identification of individual gene haplotypes is prerequisite to detecting predispositions to multifactorial diseases. The level of serum 8-oxoguanine is an indicator of genotoxic stress underlying many pathologies.Objectives. A study of associations of mmp12 gene’s polymorphic variant rs652438 and the nature of genome oxidative damage in bronchial asthma.Methods. Genotyping of polymorphic variant rs652438 of gene mmp12 was performed using TaqMan-probe real-time PCR assays. The gene variant association with disease was assessed by odds ratio. The degree of DNA oxidative damage was estimated by 8-oxoguanine serum concentrations determined in monoclonal antibody-based enzyme immunoassays. The StatPro software package with StatTools (Palisade Corporation, USA) was used for statistical data processing.Results. The haplotype and allele frequencies were established for polymorphic locus rs652438 of the mmp12 gene in the control and bronchial asthma cohorts. Heterozygotes were shown to differ significantly; the estimate was 2.3-fold higher in the control vs. bronchial asthma (BA) cohort (p < 0.05). The AA and GG haplotype frequencies did not differ significantly. The minor allele G odds ratio (OR = 0.362, CI 95% 0.134–0.975) suggests its protective effect. This may be associated with a lowering activity of the encoded macrophage metalloelastase enzyme, which results in a poorer extracellular matrix destruction in the bronchial tree. The baseline 8-oxoG levels in the control and BA samples were 6.4 and 9.4 ng/mL, respectively (U = 25, Ucut-off = 23; p >0.05). An in vitro electromagnetic exposure of varying frequency leads to a significant oxidative genomic damage in both cohorts and an earlier reparative depletion in bronchial asthma vs. control.Conclusion. A protective effect of minor allele G against pathology has been demonstrated. Adaptations to oxidative genomic stress in bronchial asthma manifest by an impaired resistance to in vitro high-intensity electromagnetic exposures.