Αlpha-1 Antitrypsin Gene Polymorphism in the Egyptian Population: Association with Obstructive Lung Diseases
DOI:
https://doi.org/10.17140/PRRMOJ-1-103Keywords:
Αlpha-1 antitrypsin deficiency, AAT gene polymorphism, Heterozygous PiMZ, Asthma, COPD, IL-10, IgE, Obstructive lung diseasesAbstract
Background: Given the potential adverse effects of asthma and Chronic Obstructive Pulmonary Disease (COPD), this study was undertaken to explore Alpha-1 Antitrypsin (AAT) polymor-phism 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 predis-position for progressing to COPD. Genetic counselling of patients having obstructive airway diseases is very important for diagnosis, prognosis and treatment.
References
Crystal RG, Brantly ML, Hubbard RC, Curiel DT, States DJ, Holmes MD. The alpha-1 antitrypsin gene and its mutations: clinical consequences and strategies for therapy. Chest. 1989; 95: 196-208. doi: 10.1378/chest.95.1.196
Rodriguez F, Jardí R, Costa X, et al. Rapid screening for α1- antitrypsin deficiency in patients with chronic obstructive pul-monary disease using dried blood specimens. Am J Respir Crit Care Med. 2002; 166(6): 814-817. doi: 10.1164/rccm.2203025
American Thoracic Society/European Respiratory Society statement. Standards for the diagnosis and management of in-dividuals with alpha-1 antitrypsin deficiency. Lung disease section. Am J Respir Crit Care Med. 2002; 168: 823-849. doi: 10.1164/rccm.168.7.818
Demeo DL, Silverman EK. Α 1-Antitrypsin deficiency•2: ge-netic aspects of α1-antitrypsin deficiency: phenotypes and ge-netic modifiers of emphysema risk. Thorax. 2004; 59: 259-264. doi: 10.1136/thx.2003.006502
Senn O, Russi EW, Imboden M, Probst-Hensch NM. Αlpha1- antitrypsin deficiency and lung disease: risk modification by oc-cupational and environmental inhalants. Eur Respir J. 2005; 26: 1-6. doi: 10.1183/09031936.05.00021605
Stoller JK, Smith P, Yang P, Spray J. Physical and social im-pact of alpha1-antitrypsin deficiency: results of a survey. Cleve-land Clin J Med.1994; 61: 461-467.
Barnes PJ. Immunology of asthma and chronic obstructive pulmonary disease. Nat Rev Immunol. 2008: 8: 183-192.
Gelb AF, Zamel N, Krishnan A. Physiologic similarities and differences between asthma and chronic obstructive pulmonary disease. Curr Opin Pulm Med. 2008: 14: 24-30.
Dawn L, Meo D, Edward J, et al. IL-10 polymorphisms are associated with airflow obstruction in severe α1-antitrypsin de-ficiency. Am J Respir Cell Mol Biol. 2008; 38(1): 114-120. doi:
1165/rcmb.2007-0107OC 10. Ortiz GR. Asthma diagnosis and management: a review of the updated national asthma education and prevention program treatment guidelines. The Internet Journal of Academic Physi-cian Assistants. 2009; 6: 2.
Vestbo J, Hurd SS, Agustí AG, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2013; 187: 347- 365. doi: 10.1164/rccm.201204-0596PP
Muawia S, Zidan M, Daabis R, Wagdy M. Association of cd40 genotyping and its protein expression with airway in-flammatory diseases. J Mol Biomark Diagn. 2011; 2: 115. doi: 10.4172/2155-9929.1000115
Homburger HA. The laboratory evaluation of allergic dis-ease: part 1: measurement methods for ige protein. Lab med. 1991; 22: 780-782.
Verbruggen, R. Quantitative immunoelectrophoretic meth-ods: a literature survey. Clin Chem. 1975; 21: 5-43.
Komorowski J, Jankiewicz J, Robak T, Błasińska-Morawiec M, Stepien H. Cytokine serum levels as the markers of thyroid activation in Graves’ disease. Immunol Lett. 1998; 60: 143-148. doi: 10.1016/S0165-2478(97)00151-X
Carrel RW, Lomas DA, Sidhar S, Foreman R. Αlpha 1-anti-trypsin deficiency. A conformational disease. Chest. 1996; 110: 243S-247S. doi: 10.1378/chest.110.6_Supplement.243S
Denden S, Haj Khelil A, Perrin P, et al. Αlpha 1 antitrypsin polymorphism in the tunisian population with special reference to pulmonary disease. Pathologie Biologie. 2008; 56: 106-110. doi: 10.1016/j.patbio.2007.05.003
Zaric B, Stojcevic J, Andrijevic L, et al. Relation of function-al characteristics and serum alpha-1-antitrypsin (AAT) concen-tration in patients with PiMM phenotype and chronic obstructive pulmonary disease (COPD). Eur J Intern Med. doi: 10.1016/j. ejim.2011.08.028
Spinola C, Bruges-Armas J, Pereira C, Brehm A, Spinola H. Αlpha-1-antitrypsin deficiency in Madeira (Portugal): the high-est prevalence in the world. Respir Med. 2009; 103(10): 1498- 1502. doi: 10.1016/j.rmed.2009.04.012
Edwin KS, Robert AS. Αlpha1-antitrypsin deficiency, New Engl. J. Med. 2009; 360: 2749-2757. doi: 10.1056/NEJM-cp0900449
Kumar M, Bhadoria DP, Dutta K, et al. The α1 AT and TIMP-1 Gene Polymorphism in the Development of Asthma. Comp Funct Genomics. 2012. doi: http://dx.doi.org/10.1155/2012/968267
Miravitlles M, Vila S, Torrella M, et al. Influence of deficient α1-anti-trypsin phenotypes on clinical characteristics and sever-ity of asthma in adults. Respiratory Medicine. 2002; 96(3): 186- 192. doi: 10.1053/rmed.2001.1237
Eden E, Strange C, Holladay B, Xie L. Asthma and al-lergy in alpha-1 antitrypsin deficiency. Respiratory Medicine. 2006; 100(8): 1384-1391. doi: http://dx.doi.org/10.1016/j. rmed.2005.11.017
AdereleWI, Ojo C, Osanyintuyi VO, Oduwole O. “Serum alpha-1-antitrypsin level in asthmatic children”. African Journal of Medicine and Medical Sciences. 1985; 14(3-4): 161-167.
Vignola AM, Bonanno A, Profita M, et al. Effect of age and asthma duration upon elastase and a1- antitrypsin lev-els in adult asthmatics. Eur Respir J. 2003; 22: 795-801. doi: 10.1183/09031936.03.00112302
Dalo B, Herbeth B, Bagrel A, Siest G. Study of factors of biological variations acting on the concentration of the alpha-1-serous antitrypsin in a common population. Ann Biol Clin (Paris). 1981; 39: 121-126.
Eden E, Mitchell D, Mehlman B, et al. Atopy, asthma, and emphysema in patients with severe α-1-antitrypsin deficiency. Am J Respir Crit Care Med. 1997; 156: 68-74. doi: 10.1164/ ajrccm.156.1.9508014
O Donnell R, Breen D, Wilson S, Djukanovic R. Inflamma-tory cells in the airways in COPD. Thorax. 2006; 61: 448-454. doi: 10.1136/thx.2004.024463
Weiss EBA, Mamelak AJ, La Morgia S, et al. The role of interleukin-10 in the pathogenesis and potential treatment of skin diseases. J Am Acad Dermatol. 2004; 657-675. doi: http:// dx.doi.org/10.1016/j.jaad.2003.11.075
Trinchieri G, Scoot P. Interleukin-12: a proinflammatory cy-tokine with immunoregulatory functions. Research in Immunol-ogy. 1995; 146(7-8): 423-431.
Fiorentino DF, Zlotnik A, Vieira P, et al. IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1- cells. Journal of Immunology. 1991; 146(10): 3444-3451.
Takahashi H, Nukiwa T, Ogushi SF, et al. Characterization of the gene and protein of the α1-antitrypsin deficiency allele M (procida). The Journal of Biological Chemistry. 1988; 263: 30: 15528-15534.
Ceyhan BB, Enc FY, Sahin S. IL-2 and IL-10 levels in in-duced sputum and serum samples of asthmatics. Journal of Investigational Allergology and Clinical Immunology. 2004; 14(1): 80-85.
Bhadoria P, Kumar M, Deshmukh A, et al. Inflammatory Cy-tokines In Indian Patients Of Chronic Obstructive Pulmonary Disorder. Chronic Obstructive Pulmonary Disease Pathogen-esis. 2013; 33: A4075.
Dow L, Coggon D, Campbell MJ, Osmond C, Holgate ST. The interaction between immunoglobin-E and smoking in air-flow obstruction in the elderly. Am Rev Respir Dis. 1992; 146: 402-407. doi: 10.1164/ajrccm/146.2.402
Villar M, Tracey A, Dow L, Coggon D, Lampe FC, Holgate ST. The influence of bronchial responsiveness, atopy, and serum IgE on the decline in FEV . A longitudinal study in the elderly. Am J Respir Crit Care Med. 1995; 151: 656-662. doi: 10.1164/ ajrccm/151.3_Pt_1.656
Platts-Mills TA, Thomas WR, Aalberse RC, Vervloet D, Champman MD. Dust mite allergens and asthma: report of a second international workshop. J Allergy Clin Immunol. 1992; 89: 1046-1060.
Downloads
Published
How to Cite
Issue
Section
License
This work is licensed under a Creative Commons Attribution 4.0 International License.
All content published in Pulmonary Research and Respiratory Medicine (PRRM) is licensed under the Creative Commons Attribution 4.0 International License (CC BY 4.0). This license allows anyone to copy, distribute, transmit, and adapt the work — including for commercial purposes — provided appropriate credit is given to the original author(s) and source.
