Arif Bashir1, Younis M Hazari2, Samirul Bashir1, Nazia Hilal1, Mariam Banday1, Mir Khurshid Iqbal1, Tariq Rashid Jan3, Syed Suraiya Farooq4, Naveed Nazir Shah5, Khalid Majid Fazili6. 1. Department of Biotechnology, University of Kashmir, Srinagar, J&K, 190006, India. 2. Institute of Biomedical Sciences, University of Chile, 8380453, Santiago, Chile. 3. Department of Statistics, University of Kashmir, Srinagar, J&K, 190006, India. 4. Department of Chest Medicine, Government Medical College, Srinagar, J&K, 190006, India. 5. Department of Chest Medicine, Government Medical College, Srinagar, J&K, 190006, India. naveednazirshah@yahoo.com. 6. Department of Biotechnology, University of Kashmir, Srinagar, J&K, 190006, India. fazili@kashmiruniversity.ac.in.
Abstract
PURPOSE: Different mutations in coding and non-coding sequences of the SERPINA1 gene have been implicated in the pathogenesis of COPD. However, - 10T/C mutation in the hepatocyte-directed promoter region has not been associated with COPD pathogenesis so far. Here, we report an increased frequency of - 10C genotype that is associated with decreased levels of serum alpha1-antitrypsin (α1AT) in COPD patients. METHODS: The quantification of serum α1AT was done by ELISA, the phenol-chloroform method was used for DNA extraction, PCR products were directly sequenced. The IBM SPSS Statistics v21 software was used for statistical analyses of the data. RESULTS: The mean serum α1AT level was found to be 1.203+0.239 and 3.162+0.160 g/L in COPD cases and in control, respectively. The - 10C allele is associated with an increased risk of COPD [OR, 3.50 (95%CI, 1.86-6.58); p < 0.001]. The combined variant genotype (TT+CC) was significantly found associated with an increased risk of COPD [OR, 3.20 (95% CI, 1.47-6.96); p = 0.003]. A significant association of the family history with COPD (overall p value= 0.0331) suggests that genetics may play an important role in the pathogenesis of COPD. CONCLUSION: The polymorphism associated with hepatocyte-specific promoter region (- 10T/C) is likely to be associated with the pathogenesis of COPD. It is quite possible that the change of the base in the hepatocyte-specific promoter of the SERPINA1 gene can modulate its strength, thereby driving the reduced expression of α1AT.
PURPOSE: Different mutations in coding and non-coding sequences of the SERPINA1 gene have been implicated in the pathogenesis of COPD. However, - 10T/C mutation in the hepatocyte-directed promoter region has not been associated with COPD pathogenesis so far. Here, we report an increased frequency of - 10C genotype that is associated with decreased levels of serum alpha1-antitrypsin (α1AT) in COPD patients. METHODS: The quantification of serum α1AT was done by ELISA, the phenol-chloroform method was used for DNA extraction, PCR products were directly sequenced. The IBM SPSS Statistics v21 software was used for statistical analyses of the data. RESULTS: The mean serum α1AT level was found to be 1.203+0.239 and 3.162+0.160 g/L in COPD cases and in control, respectively. The - 10C allele is associated with an increased risk of COPD [OR, 3.50 (95%CI, 1.86-6.58); p < 0.001]. The combined variant genotype (TT+CC) was significantly found associated with an increased risk of COPD [OR, 3.20 (95% CI, 1.47-6.96); p = 0.003]. A significant association of the family history with COPD (overall p value= 0.0331) suggests that genetics may play an important role in the pathogenesis of COPD. CONCLUSION: The polymorphism associated with hepatocyte-specific promoter region (- 10T/C) is likely to be associated with the pathogenesis of COPD. It is quite possible that the change of the base in the hepatocyte-specific promoter of the SERPINA1 gene can modulate its strength, thereby driving the reduced expression of α1AT.
Authors: Younis Mohammad Hazari; Arif Bashir; Mudasir Habib; Samirul Bashir; Huma Habib; M Abul Qasim; Naveed Nazir Shah; Ehtishamul Haq; Jeffrey Teckman; Khalid Majid Fazili Journal: Mutat Res Rev Mutat Res Date: 2017-03-18 Impact factor: 5.657
Authors: J Gupta; D P Bhadoria; M K Lal; R Kukreti; D Chattopadhaya; V K Gupta; R Dabur; V Yadav; A K Chhillar; G L Sharma Journal: Clin Biochem Date: 2005-05 Impact factor: 3.281
Authors: Peter Burney; Anamika Jithoo; Bernet Kato; Christer Janson; David Mannino; Ewa Nizankowska-Mogilnicka; Michael Studnicka; Wan Tan; Eric Bateman; Ali Koçabas; William M Vollmer; Thorarrin Gislason; Guy Marks; Parvaiz A Koul; Imed Harrabi; Louisa Gnatiuc; Sonia Buist Journal: Thorax Date: 2013-12-18 Impact factor: 9.139