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Combinatorial effect ofTIMP-1andα1ATgene polymorphisms on development of chronic obstructive pulmonary disease

Elsevier Inc.
Publication Date
DOI: 10.1016/j.clinbiochem.2011.06.986
  • Alpha-1 Antitrypsin
  • Tissue Inhibitor Of Metalloproteinase-1
  • Gene Interaction
  • Chronic Obstructive Pulmonary Disease
  • Biology


Abstract Objective To study the role of α 1 AT and TIMP-1 gene polymorphisms in development of COPD. Design and methods Blood samples from total 408 subjects (217 COPD patients and 191 controls) were used for genotyping and estimating biolevels of α 1AT, TIMP-1 and inflammatory cytokines. Data was analyzed to determine the role of interaction of TIMP-1 and α 1 AT genes; and interplay between various genotypes and biolevels of α 1AT, TIMP-1 and inflammatory cytokines in development of COPD. Results Significantly low levels of α 1AT and TIMP-1 were observed in COPD patients as compared to controls (P = 0.001), where as the inflammatory cytokines were found to be increased in patients. PIM3 allele of α 1 AT gene in COPD patients was found to be associated with low levels of α 1AT (P = 0.001), the effect being more pronounced when PIM3 combined with rs6609533 of TIMP-1 gene (P = 0.0001). Combination of genotypes rs6609533 of TIMP-1 and PIM3 of α 1 AT containing the risk alleles was over-represented in patients (P = 0.005). Conclusion The SNP rs6609533 of TIMP-1 gene interacted with PIM3 of α 1 AT to make a possible risk combination for development of COPD.

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