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- Title
SERPINA1 Hepatocyte-Specific Promoter Polymorphism Associate with Chronic Obstructive Pulmonary Disease in a Study of Kashmiri Ancestry Individuals.
- Authors
Bashir, Arif; Hazari, Younis M.; Bashir, Samirul; Hilal, Nazia; Banday, Mariam; Iqbal, Mir Khurshid; Jan, Tariq Rashid; Farooq, Syed Suraiya; Shah, Naveed Nazir; Fazili, Khalid Majid
- 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.
- Subjects
OBSTRUCTIVE lung diseases; LIVER cells; GENETIC mutation; GENOTYPES; ENZYME-linked immunosorbent assay; QUANTITATIVE research
- Publication
Lung, 2018, Vol 196, Issue 4, p447
- ISSN
0341-2040
- Publication type
Article
- DOI
10.1007/s00408-018-0124-8