Combinatorial effect of TIMP-1 and α1AT gene polymorphisms on development of chronic obstructive pulmonary disease

ObjectiveTo study the role of α1AT and TIMP-1 gene polymorphisms in development of COPD.Design and methodsBlood samples from total 408 subjects (217 COPD patients and 191 controls) were used for genotyping and estimating biolevels of α1AT, TIMP-1 and inflammatory cytokines. Data was analyzed to determine the role of interaction of TIMP-1 and α1AT genes; and interplay between various genotypes and biolevels of α1AT, TIMP-1 and inflammatory cytokines in development of COPD.ResultsSignificantly low levels of α1AT 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 α1AT gene in COPD patients was found to be associated with low levels of α1AT (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 α1AT containing the risk alleles was over-represented in patients (P = 0.005).ConclusionThe SNP rs6609533 of TIMP-1 gene interacted with PIM3 of α1AT to make a possible risk combination for development of COPD.