Investigating the Association of Orosomucoid 1-like 3 (ORMDL3) Gene Polymorphism (rs12603332) with Susceptibility to Allergic Asthma in Iranian Northwestern Azeri Population
AbstractOrosomucoid 1-like 3 (ORMDL3) gene, located on chromosome 17q21, is an asthma candidate gene that encodes ORMDL3. This molecule has been reported to play a role in airway remodeling and bronchial hyper-responsiveness. In this study, we aimed to investigate the possible association of ORMDL3 single nucleotide polymorphism (SNP) (rs12603332) with susceptibility to allergic asthma in Iranian Northwestern Azeri population. 193 asthmatic patients and 185 normal individuals were included. Genomic DNA was extracted and genotyping was performed by standard restriction fragment length polymorphism-polymerase chain reaction RFLP-PCR method using BstUI restriction enzyme. Our results showed dominant presence of TC genotype and C allele in both patients (49.2% and 59.8%, respectively) and controls (48.6% and 60%, respectively). Frequency of genotypes and alleles showed no significant difference between two groups (p=0.994 and p=1.00, respectively). None of alleles could be defined as risk allele for allergic asthma (OR=0.99, 0.88-1.12, 95% CI). We failed to show significant association between ORMDL3 rs12603332 with predisposition to allergic asthma in Iranian Northwestern Azeri population. More studies with larger number of participants should be done to find more reliable results for such association.
Paulenda T, Draber P. The role of ORMDL proteins, guardians of cellular sphingolipids, in asthma. Allergy. 2016;71(7):918-30.Siow DL, Wattenberg BW. Mammalian ORMDL proteins mediate the feedback response in ceramide biosynthesis. The Journal of biological chemistry. 2012;287(48):40198-204.Siow D, Sunkara M, Morris A, Wattenberg B. Regulation of de novo sphingolipid biosynthesis by the ORMDL proteins and sphingosine kinase-1. Advances in biological regulation. 2015;57:42-54.Berce V, Kozmus CE, Potocnik U. Association among ORMDL3 gene expression, 17q21 polymorphism and response to treatment with inhaled corticosteroids in children with asthma. The pharmacogenomics journal. 2013;13(6):523-9.Balantic M, Rijavec M, Flezar M, Camlek T, Hudoklin I, Kosnik M et al. A polymorphism in ORMDL3 is associated not only with asthma without rhinitis but also with chronic obstructive pulmonary disease. Journal of investigational allergology & clinical immunology. 2013;23(4):256-61.Miller M, Tam AB, Mueller JL, Rosenthal P, Beppu A, Gordillo R. Cutting Edge: Targeting Epithelial ORMDL3 Increases, Rather than Reduces, Airway Responsiveness and Is Associated with Increased Sphingosine-1-Phosphate. 2017;198(8):3017-22.Miller M, Rosenthal P, Beppu A, Gordillo R, Broide DH. Oroscomucoid like protein 3 (ORMDL3) transgenic mice have reduced levels of sphingolipids including sphingosine-1-phosphate and ceramide. The Journal of allergy and clinical immunology. 2017;139(4):1373-6.e4.Oyeniran C, Sturgill JL, Hait NC, Huang WC, Avni D, Maceyka M et al. Aberrant ORM (yeast)-like protein isoform 3 (ORMDL3) expression dysregulates ceramide homeostasis in cells and ceramide exacerbates allergic asthma in mice. The Journal of allergy and clinical immunology. 2015;136(4):1035-46.e6.Sleiman PM, Annaiah K, Imielinski M, Bradfield JP, Kim CE, Frackelton EC et al. ORMDL3 variants associated with asthma susceptibility in North Americans of European ancestry. The Journal of allergy and clinical immunology. 2008;122(6):1225-7.Qiu R, Yang Y, Zhao H, Li J, Xin Q, Shan S et al. Signal transducer and activator of transcription 6 directly regulates human ORMDL3 expression. The FEBS journal. 2013;280(9):2014-26.Zhuang LL, Huang BX, Feng J, Zhu LH, Jin R, Qiu LZ et al. All-trans retinoic acid modulates ORMDL3 expression via transcriptional regulation. PloS one. 2013;8(10):e77304.Carreras-Sureda A, Cantero-Recasens G, Rubio-Moscardo F, Kiefer K, Peinelt C, Niemeyer BA et al. ORMDL3 modulates store-operated calcium entry and lymphocyte activation. Human molecular genetics. 2013;22(3):519-30.Ha SG, Ge XN, Bahaie NS, Kang BN, Rao A, Rao SP et al. ORMDL3 promotes eosinophil trafficking and activation via regulation of integrins and CD48. Nature communications. 2013;4:2479.Pranculiene G, Steponaitiene R, Skieceviciene J, Kucinskiene R, Kiudelis G, Adamonis K et al. Associations between NOD2, IRGM and ORMDL3 polymorphisms and pediatric-onset inflammatory bowel disease in the Lithuanian population. Medicina (Kaunas, Lithuania). 2016;52(6):325-30.Ma X, Qiu R, Dang J, Li J, Hu Q, Shan S et al. ORMDL3 contributes to the risk of atherosclerosis in Chinese Han population and mediates oxidized low-density lipoprotein-induced autophagy in endothelial cells. Scientific reports. 2015;5:17194.Tomita K, Sakashita M, Hirota T, Tanaka S, Masuyama K, Yamada T et al. Variants in the 17q21 asthma susceptibility locus are associated with allergic rhinitis in the Japanese population. Allergy. 2013;68(1):92-100.Hsu KJ, Turvey SE. Functional analysis of the impact of ORMDL3 expression on inflammation and activation of the unfolded protein response in human airway epithelial cells. Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology. 2013;9(1):4.Komi DE, Kazemi T, Bussink AP. New Insights Into the Relationship Between Chitinase-3-Like-1 and Asthma. Current allergy and asthma reports. 2016;16(8):57.Ono JG, Worgall TS, Worgall S. 17q21 locus and ORMDL3: an increased risk for childhood asthma. Pediatric research. 2014;75(1-2):165-70.Tajik N, Kazemi T, Delbandi A, Ghods A, Salek Moghaddam A. The Predictive Value of HLA-DR Matching and Cytokine Gene Polymorphisms in Renal Allograft Acute Rejection: a Living-unrelated Donor (LURD) Study. Iranian journal of immunology : IJI. 2006;3(4):150-6.Fang Q, Zhao H, Wang A, Gong Y, Liu Q. Association of genetic variants in chromosome 17q21 and adult-onset asthma in a Chinese Han population. BMC medical genetics. 2011;12:133.Lluis A, Schedel M, Liu J, Illi S, Depner M, von Mutius E et al. Asthma-associated polymorphisms in 17q21 influence cord blood ORMDL3 and GSDMA gene expression and IL-17 secretion. The Journal of allergy and clinical immunology. 2011;127(6):1587-94.e6.Jin R, Yuan WX, Xu HG, Ren W, Zhuang LL, Zhou GP. Characterization of a novel isoform of the human ORMDL3 gene. Cell and tissue research. 2011;346(2):203-8.Jang Y, Lee AY, Kim JE, Jeong SH, Kim JS, Cho MH. Benomyl-induced effects of ORMDL3 overexpression via oxidative stress in human bronchial epithelial cells. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2016;98(Pt B):100-6.Schedel M, Michel S, Gaertner VD, Toncheva AA, Depner M, Binia A et al. Polymorphisms related to ORMDL3 are associated with asthma susceptibility, alterations in transcriptional regulation of ORMDL3, and changes in TH2 cytokine levels. The Journal of allergy and clinical immunology. 2015;136(4):893-903.e14.Ferreira MA, McRae AF, Medland SE, Nyholt DR, Gordon SD, Wright MJ et al. Association between ORMDL3, IL1RL1 and a deletion on chromosome 17q21 with asthma risk in Australia. European journal of human genetics : EJHG. 2011;19(4):458-64.Wu H, Romieu I, Sienra-Monge JJ, Li H, del Rio-Navarro BE, London SJ. Genetic variation in ORM1-like 3 (ORMDL3) and gasdermin-like (GSDML) and childhood asthma. Allergy. 2009;64(4):629-35.Kavalar MS, Balantic M, Silar M, Kosnik M, Korosec P, Rijavec M. Association of ORMDL3, STAT6 and TBXA2R gene polymorphisms with asthma. International journal of immunogenetics. 2012;39(1):20-5.Zhao YF, Luo YM, Xiong W, Wu XL. Genetic variation in ORMDL3 gene may contribute to the risk of asthma: a meta-analysis. Human immunology. 2014;75(9):960-7.Zhai WH, Song CY, Huang ZG, Sha H. Correlation between the genetic polymorphism of ORMDL3 gene and asthma risk: a meta-analysis. Genetics and molecular research : GMR. 2015;14(2):7101-12.Shi H, Cheng D, Yi L, Huo X, Zhang K, Zhen G. Association between ORMDL3 polymorphism and susceptibility to asthma: a meta-analysis. International journal of clinical and experimental medicine. 2015;8(3):3173-83.Hrdlickova B, Holla LI. Relationship between the 17q21 locus and adult asthma in a Czech population. Human immunology. 2011;72(10):921-5.Galanter J, Choudhry S, Eng C, Nazario S, Rodriguez-Santana JR, Casal J et al. ORMDL3 gene is associated with asthma in three ethnically diverse populations. American journal of respiratory and critical care medicine. 2008;177(11):1194-200.Zhao CN, Fan Y, Huang JJ, Zhang HX, Gao T, Wang C et al. The Association of GSDMB and ORMDL3 Gene Polymorphisms With Asthma: A Meta-Analysis. Allergy, asthma & immunology research. 2015;7(2):175-85