Generic placeholder image

Endocrine, Metabolic & Immune Disorders - Drug Targets

Author(s): Wesam Kooti, Mohammad Abdi, Yashpal S. Malik, Bijan Nouri, Ali Jalili, Mohammad A. Rezaee, Mohammad R. Rahmani* and Rasoul N. Kalmarzi*

DOI: 10.2174/1872214812666190527104329

DownloadDownload PDF Flyer Cite As
Association of CYP2C19 and HSP70 Genes Polymorphism with Aspirin- Exacerbated Respiratory Disease in a Kurd Population

Page: [256 - 262] Pages: 7

  • * (Excluding Mailing and Handling)

Abstract

Background: CYP2C19 a metabolizing enzyme and Heat Shock Proteins (HSP) are induced in stress conditions, such as hypoxia and ischemia. Recently, polymorphism in the CYP2C19 and HSP genes has been established in Aspirin-Exacerbated Respiratory Disease (AERD).

Objective: We investigated the polymorphism of these two genes in Kurdish patients with AERD.

Methods: This study involved 306 subjects, referred to the Be’sat hospital in Kurdistan Province, which were divided into three groups, (i) Aspirin Induced Asthma (AIA), (ii) Aspirin Tolerant Asthma (ATA), and (iii) healthy subjects as control. The subjects as control and ATA\AIA groups were verified by the physician. The demographic data of each subject with respect to age, sex, parental education, and residence was collected. Spirometry was performed on subjects and blood samples were collected for serum Immunoglobulin E (IgE) estimation and molecular tests. Genotyping was done for CYP2C19 681G>A، CYP2C19 636G>A, and HSPA1B1267A>G by using PCR- Restriction Fragment Length Polymorphism (RFLP) and for HSPA1B-179C>T by High Resolution Melting (HRM).

Results: Demographic statistics were not significantly different between the three groups (p>0.05). Further, genotypes were also not observed to be significantly different in the genes of CYP2C19 681G>A, CYP2C19 636G>A and HSPA1B1267A>G (p>0.05). However, the heterozygote genotype in HSPA1B-179 C>T in AIA group was higher than the control group (p<0.05). Notably, 92.8 % of the subjects showed heterozygote genotype in HSPA1B1267 A>G. In clinical tests, FEV-1, FVC, and asthma severity in the AIA group were higher than control and additionally IgE levels were lower in this group (p<0.05).

Conclusion: The results confirm the association of polymorphism in the HSPA1B-179C>T and HSPA1B1267A>G with AERD in the Kurdish population.

Keywords: Polymorphism, PCR-RFLP, HRM, aspirin-exacerbated respiratory disease, heat shock proteins, asthma, kurdistan.

Graphical Abstract

[1]
Clifford, R.L.; Knox, A.J. Vitamin D - a new treatment for airway remodelling in asthma? Br. J. Pharmacol., 2009, 158(6), 1426-1428.
[http://dx.doi.org/10.1111/j.1476-5381.2009.00429.x] [PMID: 19906117]
[2]
Shin, S-W.; Park, J.; Kim, Y-J.; Uh, S.T.; Choi, B.W.; Kim, M.K.; Choi, I.S.; Park, B.L.; Shin, H.; Park, C.S. A highly sensitive and specific genetic marker to diagnose aspirin-exacerbated respiratory disease using a genome-wide association study. DNA Cell Biol., 2012, 31(11), 1604-1609.
[http://dx.doi.org/10.1089/dna.2012.1688] [PMID: 22994212]
[3]
Pasaje, C.F.A.; Bae, J.S.; Park, B-L.; Cheong, H.S.; Jang, A-S.; Uh, S-T.; Kim, M.K.; Koh, I.S.; Kim, J.H.; Park, T.J.; Lee, J.S.; Kim, Y.; Park, C.S.; Shin, H.D. Association analysis of C6 genetic variations and aspirin hypersensitivity in Korean asthmatic patients. Hum. Immunol., 2011, 72(10), 973-978.
[http://dx.doi.org/10.1016/j.humimm.2011.05.022] [PMID: 21704099]
[4]
Kim, H-J.; Cho, S-H.; Park, J-S.; Lee, T-H.; Lee, E-J.; Kim, Y-H.; Uh, S.T.; Chung, I.Y.; Kim, M.K.; Choi, I.S.; Park, B.L.; Shin, H.D.; Park, C.S. Association analysis of formyl peptide receptor 2 (FPR2) polymorphisms and aspirin exacerbated respiratory diseases. J. Hum. Genet., 2012, 57(4), 247-253.
[http://dx.doi.org/10.1038/jhg.2012.12] [PMID: 22377711]
[5]
Kohyama, K.; Abe, S.; Kodaira, K.; Yukawa, T.; Hozawa, S.; Morioka, J.; Inamura, H.; Ota, M.; Sagara, H.; Kurosawa, M. Polymorphisms of the CYP2C19 gene in Japanese patients with aspirin-exacerbated respiratory disease. J. Allergy Clin. Immunol., 2011, 128(5), 1117-1120.
[http://dx.doi.org/10.1016/j.jaci.2011.07.013] [PMID: 21855977]
[6]
Choi, J-H.; Park, H-S.; Oh, H-B.; Lee, J-H.; Suh, Y-J.; Park, C-S.; Shin, H.D. Leukotriene-related gene polymorphisms in ASA-intolerant asthma: an association with a haplotype of 5-lipoxygenase. Hum. Genet., 2004, 114(4), 337-344.
[http://dx.doi.org/10.1007/s00439-004-1082-1] [PMID: 14749922]
[7]
Van Sambeek, R.; Stevenson, D.D.; Baldasaro, M.; Lam, B.K.; Zhao, J.; Yoshida, S.; Yandora, C.; Drazen, J.M.; Penrose, J.F. 5′ flanking region polymorphism of the gene encoding leukotriene C4 synthase does not correlate with the aspirin-intolerant asthma phenotype in the United States. J. Allergy Clin. Immunol., 2000, 106(1 Pt 1), 72-76.
[http://dx.doi.org/10.1067/mai.2000.107603] [PMID: 10887308]
[8]
Higashi, N.; Mita, H.; Ono, E.; Fukutomi, Y.; Yamaguchi, H.; Kajiwara, K. Profile of eicosanoid generation in aspirin-intolerant asthma and anaphylaxis assessed by new biomarkers. Journal of Allergy and Clinical Immunology., 2010, 125(5), 1084-1091.e6.
[http://dx.doi.org/10.1016/j.jaci.2009.12.977]
[9]
Kikuchi, K.; Abe, S.; Kodaira, K.; Yukawa, T.; Hozawa, S.; Mochizuki, H.; Kurosawa, M. Heat shock protein 70 gene polymorphisms in Japanese patients with aspirin-exacerbated respiratory disease. J. Investig. Med., 2013, 61(4), 708-714.
[http://dx.doi.org/10.2310/JIM.0b013e3182857d6c] [PMID: 23392055]
[10]
Yildirim Yaroğlu, H.; Calikoğlu, M.; Tamer Gümüş, L. CYP2C19 gene polymorphism may be a risk factor for bronchial asthma. Med. Princ. Pract., 2011, 20(1), 39-42.
[http://dx.doi.org/10.1159/000322077] [PMID: 21160212]
[11]
Palikhe, N.S.; Kim, S-H.; Nam, Y.H.; Ye, Y-M.; Park, H-S. Polymorphisms of Aspirin-Metabolizing Enzymes CYP2C9, NAT2 and UGT1A6 in Aspirin-Intolerant Urticaria. Allergy Asthma Immunol. Res., 2011, 3(4), 273-276.
[http://dx.doi.org/10.4168/aair.2011.3.4.273] [PMID: 21966608]
[12]
Aron, Y.; Busson, M.; Polla, B.S.; Dusser, D.; Lockhart, A.; Swierczewski, E.; Favatier, F. Analysis of hsp70 gene polymorphism in allergic asthma. Allergy, 1999, 54(2), 165-170.
[http://dx.doi.org/10.1034/j.1398-9995.1999.00859.x] [PMID: 10221440]
[13]
Ramakrishna, K.; Pugazhendhi, S.; Kabeerdoss, J.; Peter, J.V. Association between heat shock protein 70 gene polymorphisms and clinical outcomes in intensive care unit patients with sepsis. Indian J. Crit. Care Med., 2014, 18(4), 205-211.
[http://dx.doi.org/10.4103/0972-5229.130571] [PMID: 24872649]
[14]
Waterer, G.W.; ElBahlawan, L.; Quasney, M.W.; Zhang, Q.; Kessler, L.A.; Wunderink, R.G. Heat shock protein 70-2+1267 AA homozygotes have an increased risk of septic shock in adults with community-acquired pneumonia. Crit. Care Med., 2003, 31(5), 1367-1372.
[http://dx.doi.org/10.1097/01.CCM.0000063088.86079.03] [PMID: 12771604]
[15]
Ikwegbue, P.C.; Masamba, P.; Oyinloye, B.E.; Kappo, A.P. Roles of Heat Shock Proteins in Apoptosis, Oxidative Stress, Human Inflammatory Diseases, and Cancer. Pharmaceuticals (Basel), 2017, 11(1)E2
[http://dx.doi.org/10.3390/ph11010002] [PMID: 29295496]