Manish Kumar1, D P Bhadoria2, Koushik Dutta3, Seema Singh4, Jyotsana Gupta5, Ram Kumar6, Anil K Chhillar7, Vibha Yadav8, Bharat Singh9, G L Sharma10. 1. 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. 2. Maulana Azad Medical College and Lok Nayak Jaiprakash Narayan Hospital New Delhi-110002, India. Electronic address: dharampbhadoria@yahoo.co.in. 3. Maulana Azad Medical College and Lok Nayak Jaiprakash Narayan Hospital New Delhi-110002, India. Electronic address: sriduttakoushik@yahoo.com. 4. 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. 5. Research Institute of the McGill University Health Centre, Montréal QC, Canada, H3G 1A4. Electronic address: jyotsanagupta4@gmail.com. 6. Institute of Genomics and Integrative Biology, University Campus, Mall Road Delhi-110007, India. Electronic address: ramkumarbu@gmail.com. 7. Centre for Biotechnology, M. D. University, Rohtak, Haryana-124001, India. Electronic address: anil.chhillar@gmail.com. 8. National Institute of Health, Rockville Pike, Bethesda, MD 20892, USA. Electronic address: vibhabio@gmail.com. 9. Institute of Genomics and Integrative Biology, University Campus, Mall Road Delhi-110007, India. Electronic address: bharatsingh1601@gmail.com. 10. Institute of Genomics and Integrative Biology, University Campus, Mall Road Delhi-110007, India. Electronic address: drglsharma@hotmail.com.
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(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). 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.
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 COPDpatients 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 COPDpatients 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 COPDpatients 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). 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.
Authors: Manish Kumar; D P Bhadoria; Koushik Dutta; Mitesh Kumar F; Bharat Singh; Seema Singh; Anil K Chhillar; D Behera; G L Sharma Journal: Comp Funct Genomics Date: 2012-11-21
Authors: Leonardo Lorente; Mar Martín; Fátima Plasencia; Jordi Solé-Violán; José Blanquer; Lorenzo Labarta; César Díaz; Juan María Borreguero-León; Alejandro Jiménez; José Antonio Páramo; Josune Orbe; José A Rodríguez; Eduardo Salido Journal: Crit Care Date: 2013-05-25 Impact factor: 9.097