The α1AT and TIMP-1 Gene Polymorphism in the Development of Asthma

Comparative and Functional Genomics
Volume 2012 (2012), Article ID 968267, 10 pages
doi:10.1155/2012/968267

Clinical Study

The α₁AT and TIMP-1 Gene Polymorphism in the Development of 

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Asthma

Manish Kumar,^1,2 D. P. Bhadoria,³ Koushik Dutta,³ Mitesh Kumar F.,³ Bharat Singh,¹ Seema Singh,¹ Anil K. Chhillar,² D. Behera,⁴ and G. L. Sharma¹

¹CSIR-Institute of Genomics and Integrative Biology, University Campus, Mall Road, Delhi 110007, India
²Centre for Biotechnology, Maharshi Dayanand University, Rohtak, Haryana 124001, India
³Maulana Azad Medical College and Lok Nayak Jai Prakash Narayan Hospital, New Delhi 110002, India
⁴Lala Ram Sarup Institute of Tuberculosis and Respiratory Diseases, New Delhi 110030, India

Received 2 August 2012; Accepted 13 October 2012

Academic Editor: G. Pesole

Copyright © 2012 Manish Kumar et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Asthma has been an inflammatory disorder accompanied by tissue remodeling and protease-antiprotease imbalance in lungs. The SNPs of alpha-1 antitrypsin (α₁AT) and tissue inhibitor of metalloproteinase-1 (TIMP-1) genes were studied for their association with asthma. Genotyping of α₁ATand TIMP-1 genes was performed in 202 asthmatics and 204 controls. Serum levels of α₁AT, 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 α₁AT 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 α₁AT gene. The novel SNP Glu363Lys of α₁AT was found to be associated with asthma (). The analysis ofTIMP-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 α₁AT and G3774A and Phe124Phe of TIMP-1 could be important genetic markers for use in better management of the disease.