The α(1)AT and TIMP-1 Gene Polymorphism in the Development of Asthma.

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(1)AT, 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(1)AT 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.