Αlpha-1 Antitrypsin Gene Polymorphism in the Egyptian Population: Association with Obstructive Lung Diseases

Abstract

Background: Given the potential adverse effects of asthma and Chronic Obstructive Pulmonary Disease (COPD), this study was undertaken to explore Alpha-1 Antitrypsin (AAT) polymorphism in the Egyptian population and its role in the development and/ or progression of asthma and COPD. The identification of IL-10 as a potential modifier gene for COPD susceptibility provided insight into additional inflammatory pathways to consider in AAT deficiency. Methods: This study was carried on 90 unrelated Egyptians; 37 asthmatics, 33 COPD patients and 20 controls. Patients were evaluated clinically and with spirometry. The frequency of AAT gene polymorphism was assessed by real-time PCR. Serum levels of AAT protein, IL-10 and IgE were estimated. Results: PiZ allele was found in COPD and asthma patients as well as controls. While PiS allele was never shown up in all the groups. The prevalence of PiZ was higher in asthma and COPD than in controls (75.75%, 72.7% and 50% respectively). Serum AAT was significantly decreased in patients with asthma and COPD. Patients with the PiZ allele, despite having lower values of the serum AAT, this difference was not significant. Serum AAT was significantly correlated with severity of airflow obstruction in both asthma and COPD. There was a significant elevation of serum IgE in COPD patients carrying PiZ allele. Serum IL-10 was significantly higher in asthma and COPD patients than the controls. There was a positive significant correlation between IL-10 and IgE in COPD patients. Conclusion: The z allele frequency in the Egyptian population is higher among asthmatic and COPD patients, suggesting that it could in fact be an underlying hidden risk factor for the development of these diseases. Asthmatics carrying this deficient allele have a genetic predisposition for progressing to COPD. Genetic counselling of patients having obstructive airway diseases is very important for diagnosis, prognosis and treatment.

Lung cancer risk in workers occupationally exposed to polycyclic aromatic hydrocarbons with emphasis on the role of DNA repair gene

“…The increased frequency of mutant genotype alleles among workers with high BPDE-Alb adduct levels may be attributed to the ability of PAHs metabolites to bind to cellular proteins and DNA, resulting in cell damage and mutations (Ramesh et al 2010). A previous study on Egyptian asthmatic patients reported that the highest frequency of mutant A1AT allele was found in the patients compared to healthy control (Daabis et al 2014). Interestingly, our study was the first study that describes the association between A1AT gene mutation and the levels of PAHs adducts in exposed workers.…”