Theα₁ATandTIMP-1Gene Polymorphism in the Development of Asthma

Abstract

Asthma has been an inflammatory disorder accompanied by tissue remodeling and protease-antiprotease imbalance in lungs. The SNPs of alpha-1 antitrypsin (α 1 AT) and tissue inhibitor of metalloproteinase-1 (TIMP-1) genes were studied for their association with asthma. Genotyping of α 1 AT and TIMP-1 genes was performed in 202 asthmatics and 204 controls. Serum levels of α 1AT, TIMP-1 and cytokines were estimated to find if the interplay between genotypes and cellular biomarkers determines the pathogenesis of asthma. The analysis of results showed significantly low level of α 1AT in the serum of asthmatics as compared to controls (P = 0.001), whereas cytokines were elevated in patients. No significant difference was observed in the concentration of TIMP-1 in patients and controls. Genotyping led to the identification of 3 SNPs (Val213Ala, Glu363Lys, and Glu376Asp) in α 1 AT gene. The novel SNP Glu363Lys of α 1 AT was found to be associated with asthma (P = 0.001). The analysis of TIMP-1 gene showed the occurrence of seven SNPs, including a novel intronic SNP at base G3774A. The allele frequency of G3774A and Phe124Phe was significantly higher in asthmatics as compared to controls. Thus, the SNP Glu363Lys of α 1 AT and G3774A and Phe124Phe of TIMP-1 could be important genetic markers for use in better management of the disease.

Genetic testing of allelic variants of PIZ (GLU342Lys, RS28929474) and PIS (GLU264Val, RS17580) of SERPINA1 gene in children with bronchial asthma

“…According to numerous epidemiological studies, it has been established, that AATD is widespread in different geographical regions and is not a rare disease. In the countries of northern and western Europe, the PIZ is more common, among the countries of southern Europe, PIS is more common [24]. The PIZ allele is found in 0.1 % of the world's population.…”