title: Combinatorial effect of TIMP-1 and α1AT gene polymorphisms on development of chronic obstructive pulmonary disease.
abstract: OBJECTIVE
  To study the role of α(1)AT and TIMP-1 gene polymorphisms in development of COPD.
  
  
  METHODS
  Blood samples from total 408 subjects (217 COPD patients and 191 controls) were used for genotyping and estimating biolevels of α(1)AT, 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(1)AT, TIMP-1 and inflammatory cytokines in development of COPD.
  
  
  RESULTS
  Significantly low levels of α(1)AT 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(1)AT (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).
  
  
  CONCLUSIONS
  The SNP rs6609533 of TIMP-1 gene interacted with PIM3 of α(1)AT to make a possible risk combination for development of COPD.
authors.affiliation: Institute of Genomics and Integrative Biology, University Campus, Mall Road Delhi-110007, India; Department of Biotechnology, University of Pune, Pune-411007, India. Electronic address: manishkumarteo@gmail.com.
authors.forename: Manish
authors.initials: M
authors.lastname: Kumar
authors.affiliation: Maulana Azad Medical College and Lok Nayak Jaiprakash Narayan Hospital New Delhi-110002, India. Electronic address: dharampbhadoria@yahoo.co.in.
authors.forename: D P
authors.initials: DP
authors.lastname: Bhadoria
authors.affiliation: Maulana Azad Medical College and Lok Nayak Jaiprakash Narayan Hospital New Delhi-110002, India. Electronic address: sriduttakoushik@yahoo.com.
authors.forename: Koushik
authors.initials: K
authors.lastname: Dutta
authors.affiliation: Institute of Genomics and Integrative Biology, University Campus, Mall Road Delhi-110007, India; Department of Biotechnology, University of Pune, Pune-411007, India. Electronic address: seema.acbrdu@gmail.com.
authors.forename: Seema
authors.initials: S
authors.lastname: Singh
authors.affiliation: Research Institute of the McGill University Health Centre, Montréal QC, Canada, H3G 1A4. Electronic address: jyotsanagupta4@gmail.com.
authors.forename: Jyotsana
authors.initials: J
authors.lastname: Gupta
authors.affiliation: Institute of Genomics and Integrative Biology, University Campus, Mall Road Delhi-110007, India. Electronic address: ramkumarbu@gmail.com.
authors.forename: Ram
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Centre for Biotechnology, M. D. University, Rohtak, Haryana-124001, India. Electronic address: anil.chhillar@gmail.com.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Chhillar
authors.affiliation: National Institute of Health, Rockville Pike, Bethesda, MD 20892, USA. Electronic address: vibhabio@gmail.com.
authors.forename: Vibha
authors.initials: V
authors.lastname: Yadav
authors.affiliation: Institute of Genomics and Integrative Biology, University Campus, Mall Road Delhi-110007, India. Electronic address: bharatsingh1601@gmail.com.
authors.forename: Bharat
authors.initials: B
authors.lastname: Singh
authors.affiliation: Institute of Genomics and Integrative Biology, University Campus, Mall Road Delhi-110007, India. Electronic address: drglsharma@hotmail.com.
authors.forename: G L
authors.initials: GL
authors.lastname: Sharma
mesh_terms: D016022:Case-Control Studies; D016207:Cytokines; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007249:Inflammation / Q000276:immunology; D011110:Polymorphism, Genetic / Q000502:physiology*; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*; D000515:alpha 1-Antitrypsin / Q000235:genetics*
chemical_list: D016207:Cytokines; C043392:SERPINA1 protein, human; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D000515:alpha 1-Antitrypsin