科研之友
微信
新浪微博
Facebook
分享链接
摘要
Asthma has been an inflammatory disorder accompanied by tissue remodeling and protease-antiprotease imbalance in lungs. The SNPs of alpha-1 antitrypsin (汐1AT) and tissue inhibitor of metalloproteinase-1 (TIMP-1) genes were studied for their association with asthma. Genotyping of 汐1AT and TIMP-1 genes was performed in 202 asthmatics and 204 controls. Serum levels of 汐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 汐1AT in the serum of asthmatics as compared to controls ( ), 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 汐1AT gene. The novel SNP Glu363Lys of 汐1AT was found to be associated with asthma ( ). 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 汐1AT and G3774A and Phe124Phe of TIMP-1 could be important genetic markers for use in better management of the disease. 1. Introduction Asthma pathophysiology involves extensive remodeling of lung tissue structure, and the protease-antiprotease imbalance has been considered to play a significant role in the pathogenesis of the disease [1]. The neutrophils and alveolar macrophages (AM) synthesize neutrophil elastase (NE) and matrix metallo proteinase (MMP), respectively, which have been the prominent proteolytic enzymes released during the inflammatory events [2]. The NE is a protease which destroys major structural proteins of the alveolar wall. Since the expression and the activity of NE are required to be kept under check for the maintenance of the lung structure and integrity, an antiprotease alpha-1 antitrypsin (汐1AT) is produced in the body. The 汐1AT, primarily synthesized by hepatocytes, attenuates NE in the lungs [3]. The MMPs have been reported to play an important role in regulating a variety of cellular processes including proliferation, differentiation, migration (adhesion/dispersion), angiogenesis, host defense, and apoptosis [4, 5]. The activity of MMP-9, a major MMP present in lung tissues, is kept under tight control by the tissue inhibitor of metalloproteinase-1 (TIMP-1) [6]. It has been reported that the balance between MMP-9 and TIMP-1 gets disturbed in the
