Association of Matrix Metalloproteinases Gene Polymorphism With Clinical Manifestations of Bronchial Asthma in Children

Abstract

In the present study, we have examined association between different polymorphic variants of metalloproteinases genes and clinical manifestations of bronchial asthma in children. We observed 103 patients including 42 children with an established diagnosis of asthma. Moreover, 61 persons were examined in the control group. All patients underwent genetic testing by allele-specific polymerase chain reaction. In particular, 320A>C polymorphic locus of ММР20 gene; Val275Ala ММР20, and -8202A>G gene ММР9 were analyzed.We have found that 30 patients (71.4% of total) had bronchial asthma of mild severity, 9 children (21.4%) exhibited moderate degree, and 3 patients (7%) had severe-grade disease. Homozygous C/C variant of the polymorphic ММР20 gene, 320A>C heterozygous variant of the ММР20 Val275Ala polymorphism, and heterozygous locus of -8202A>G ММР9 gene were found to be most frequent among the children with asthma. Generally, we have observed that the frequencies of the studied alleles and genotypes did not significantly differ berween the asthma patients and children from the control group (p < 0.05). However, in patients with GGgenotype of -8202A>G ММР9 polymorphism combined with homozygosity for the C allele of ММР20 320A>C, a more severe disease was observed, being combined with polyvalent sensitization and high total IgE levels in blood serum.In conclusion, frequencies of alleles and genotypes among patients with asthma did not show any statistically significant differences from the group of healthy children. The patients homozygous for G allele of ММР9 -8202A>G polymorphism gene and for the C allele ММР20 gene (320A>C) seem to be predisposed for a more severe clinical course of the disease.

Bronchial Asthma: Genetic Factors Contributing to its Pathogenesis

“…A study by Lebedenko et al found higher frequency of homozygous C/C MMP20 gene variant with 320A>C polymorphism, heterozygous MMP20 gene variant Val275Ala, and heterozygous MMP9 gene variant with −8202A>G polymorphism in patients with BA [27]. However, the frequencies of these alleles and genotypes were not significantly different in the affected children while comparing to the healthy group.…”

“…Airway obstruction, characteristic to BA, results in impaired air movement, which not only requires additional physical effort during respiration but also induces remodeling mechanisms of the bronchopulmonary system [27]. An important role in this process is played by matrix metalloproteinases (MMPs), involved in the metabolism of proteins of the intercellular matrix.…”