Influence of Genetics Polymorphism of OATP2B1Transporter on Montelukast Response in Samples of Asthmatic Children

Authors

  • Hasnaa Haider Mohammed Department of Pharmacology and Toxicology, College of Pharmacy, University of Kerbala, Kerbela,Iraq
  • Uday Abdul-Reda Department of Pharmacology and Toxicology, College of Pharmacy, University of Al-Ameed, Kerbala, Iraq
  • Hassan Mahmood Abo-Almaali Department of Clinical Laboratory Science, College of Pharmacy, University of Kerbala ,Kerbala , Iraq
  • Akeel Mahdi Hussien Consultant Pedestrian, Kerbala Teaching Hospital of Paediatrics, Kerbala, Iraq

DOI:

https://doi.org/10.22317/jcms.v9i6.1449

Keywords:

Montelukast, Asthmatic children, OATP2B1 transporter, leukotrienes modifiers, genetics polymorphism.

Abstract

Objectives:

The primary objectives are to evaluate the impact of OATP2B1c.935G>A (rs12422149) genetic polymorphisms on montelukast treatment responses in children with asthma in Iraq.

Methods and patients:

This observational cross_sectional study was conducted from the beginning of October  2022  up to the  ending  of  September  2023  at the respiratory  clinic centre of the Karbalaa Hospital for Children.One hundred participants, both male and female, aged between six and fifteen, who had been  taking  montelukast  as  a control  medication on a  daily basis for  at least  a month, were   included in the study.Following DNA extraction, allele_specific PCR  was performed to identify the genotypes of the various patients. Measurements of total serum IgE, the Asthma Control Test(ACT), and the Pulmonary Function Tests (PEF and FEV1) were made.

Results: Genetic amplification results indicate that the distribution of the polymorphism of the c.935G>A gene was 48% in GG wild homozygous, 45% in GA mutant heterozygous, and 7% in mutant homozygous AA.

Patients with mutant genes (GA and AA) exhibit high total IgE, low  PEF and  FEV1, and  <19  ACT scores. This polymorphism is expected to have a significant association (p value<0.05)withmontelukast responsiveness.

Conclusions: 

A significant association, was  seen between the montelukast response and the OATP2B1 c.935 G>A genetic polymorphism.

References

Serebrisky D, Wiznia A. Pediatric asthma: a global epidemic. Annals of global Health. 2019;85(1).

Vos T, Flaxman AD, Naghavi M, Lozano R, et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010. The lancet. 2012 Dec 15;380(9859):2163-96.

Lee YJ, Kim CK. Montelukast use over the past 20 years: monitoring of its effects and safety issues. Clinical and Experimental Pediatrics. 2020 Oct;63(10):376.

Trinh HK, Lee SH, Cao TB, Park HS. Asthma pharmacotherapy: an update on leukotriene treatments. Expert review of respiratory medicine. 2019 Dec 2;13(12):1169-78.

Meshram D, Bhardwaj K, Rathod C, Mahady GB, Soni KK. The role of leukotrienes inhibitors in the management of chronic inflammatory diseases. Recent Patents on Inflammation & Allergy Drug Discovery. 2020 May 1;14(1):15-31.

Wermuth HR, Badri T, Takov V. Montelukast. InStatPearls [Internet] 2022 Apr 25. StatPearls Publishing.

Mooij MG, de Koning BE, Lindenbergh-Kortleve DJ, Simons-Oosterhuis Y, Van Groen BD, Tibboel D, Samsom JN, de Wildt SN. Human intestinal PEPT1 transporter expression and localization in preterm and term infants. Drug Metabolism and Disposition. 2016 Jul 1;44(7):1014-9.

Keiser M, Kaltheuner L, Wildberg C, Müller J, Grube M, Partecke LI, Heidecke CD, Oswald S. The Organic Anion–Transporting Peptide 2B1 Is Localized in the Basolateral Membrane of the Human Jejunum and Caco-2 Monolayers. Journal of Pharmaceutical Sciences. 2017 Sep 1;106(9):2657-63.

Mougey EB, Feng H, Castro M, Irvin CG, Lima JJ. Absorption of montelukast is transporter mediated: a common variant of OATP2B1 is associated with reduced plasma concentrations and poor response. Pharmacogenetics and genomics. 2009 Feb;19(2):129.

García-Menaya JM, Cordobés-Durán C, García-Martín E, Agúndez JA. Pharmacogenetic factors affecting asthma treatment response. potential implications for drug therapy. Frontiers in pharmacology. 2019 May 21;10:520.

Mougey EB, Lang JE, Wen X, Lima JJ. Effect of citrus juice and SLCO2B1 genotype on the pharmacokinetics of montelukast. The Journal of Clinical Pharmacology. 2011 May;51(5):751-60.

Kim M, Deacon P, Tirona RG, Kim RB, Pin CL, Meyer zu Schwabedissen HE, Wang R, Schwarz UI. Characterization of OATP1B3 and OATP2B1 transporter expression in the islet of the adult human pancreas. Histochemistry and cell biology. 2017 Oct;148:345-57.

Tantisira KG, Drazen JM. Genetics and pharmacogenetics of the leukotriene pathway. Journal of Allergy and Clinical Immunology. 2009 Sep 1;124(3):422-7.

Medwid S, Price HR, Taylor DP, Mailloux J, Schwarz UI, Kim RB, Tirona RG. Organic anion transporting polypeptide 2B1 (OATP2B1) genetic variants: in vitro functional characterization and association with circulating concentrations of endogenous substrates. Frontiers in Pharmacology. 2021 Sep 14;12:713567.

Li Q, Wang K, Shi HY, Wu YE, Zhou Y, Kan M, Zheng Y, Hao GX, Yang XM, Yang YL, Su LQ. Developmental pharmacogenetics of SLCO2B1 on montelukast pharmacokinetics in Chinese children. Drug design, development and therapy. 2019 Dec 27:4405-11.

Graham BL, Steenbruggen I, Miller MR, Barjaktarevic IZ, Cooper BG, Hall GL, Hallstrand TS, Kaminsky DA, McCarthy K, McCormack MC, Oropez CE. Standardization of spirometry 2019 update. An official American thoracic society and European respiratory society technical statement. American journal of respiratory and critical care medicine. 2019 Oct 15;200(8):e70-88.

Reddel HK, Bacharier LB, Bateman ED, Brightling CE, Brusselle GG, Buhl R, Cruz AA, Duijts L, Drazen JM, FitzGerald JM, Fleming LJ. Global Initiative for Asthma Strategy 2021: executive summary and rationale for key changes. American journal of respiratory and critical care medicine. 2022 Jan 1;205(1):17-35.

Ortega VE, Meyers DA. Pharmacogenetics: implications of race and ethnicity on defining genetic profiles for personalized medicine. Journal of allergy and clinical immunology. 2014 Jan 1;133(1):16-26.

McLeod HL, Evans WE. Pharmacogenomics: unlocking the human genome for better drug therapy. Annual review of pharmacology and toxicology. 2001 Apr;41(1):101-21.

Yao TC, Ou LS, Yeh KW, Lee WI, Chen LC, Huang JL, PATCH Study Group. Associations of age, gender, and BMI with prevalence of allergic diseases in children: PATCH study. Journal of Asthma. 2011 Jun 1;48(5):503-10.

Pignataro FS, Bonini M, Forgione A, Melandri S, Usmani OS. Asthma and gender: the female lung. Pharmacological research. 2017 May 1;119:384-90.

Vink NM, Postma DS, Schouten JP, Rosmalen JG, Boezen HM. Gender differences in asthma development and remission during transition through puberty: the TRacking Adolescents' Individual Lives Survey (TRAILS) study. Journal of allergy and clinical immunology. 2010 Sep 1;126(3):498-504.

Ali HJ, Kadhim HM, Al-Fahad AQ. Influence of Leukotriene Pathway Polymorphisms (Arachidonate 5-lipoxygenase ALOX5, Cysteinyl Leukotriene Receptor CysLTR1) On Response to Montelukast in A sample of Asthmatic Iraqi Patients. Journal of Pharmaceutical Negative Results. 2022 Oct 7;13(4):193-8.

Al Thamiri D, Al Kubaisy W, Ali SH. Asthma prevalence and severity among primary-school children in Baghdad. EMHJ-Eastern Mediterranean Health Journal, 11 (1-2), 79-86, 2005. 2005.

Alolayan AM, Alabeesy MS, Alqabbani AA, Almutairi AJ, Alzaidy NF, Alsaadoon SA, Alotaibi MM. Interrelationship between body mass index and asthma in children suffering from asthma-analytical cross-sectional study. European Review for Medical & Pharmacological Sciences. 2021 Aug 15;25(16).

Ungar WJ, Hadioonzadeh A, Najafzadeh M, Tsao NW, Dell S, Lynd LD. Parents and adolescents preferences for asthma control: a best-worst scaling choice experiment using an orthogonal main effects design. BMC Pulmonary Medicine. 2015 Dec;15:1-0.

Kim KA, Joo HJ, Lee HM, Park JY. SLCO2B1 genetic polymorphisms in a Korean population: pyrosequencing analyses and comprehensive comparison with other populations. Molecular biology reports. 2013 Jul;40(7):4211-7.

Laitinen A, Niemi M. Frequencies of single‐nucleotide polymorphisms of SLCO1A2, SLCO1B3 and SLCO2B1 genes in a Finnish population. Basic & clinical pharmacology & toxicology. 2011 Jan;108(1):9-13.

Kansen HM, Le TM, Uiterwaal CS, van Ewijk BE, Balemans WA, Gorissen DM, de Vries E, van Velzen MF, Slabbers GH, Meijer Y, Knulst AC. Prevalence and predictors of uncontrolled asthma in children referred for asthma and other atopic diseases. Journal of asthma and allergy. 2020 Jan 30:67-75.

Chen ZM, Zhao DY, Xiang L, Hong JG. Treatment of pediatric mild persistent asthma with low-dose budesonide inhalation suspension vs. montelukast in China. World Journal of Pediatrics. 2021 Dec;17:619-25.

Yang KD. Asthma management issues in infancy and childhood. Treatments in Respiratory Medicine. 2005 Feb;4:9-20.

Barnes N, Wei LX, Reiss TF, Leff JA, Shingo S, Yu C, Edelman JM. Analysis of montelukast in mild persistent asthmatic patients with near-normal lung function. Respiratory medicine. 2001 May 1;95(5):379-86.

Stelmach I, Grzelewski T, Bobrowska-Korzeniowska M, Stelmach P, Kuna P. A randomized, double-blind trial of the effect of anti-asthma treatment on lung function in children with asthma. Pulmonary pharmacology & therapeutics. 2007 Dec 1;20(6):691-700.

Nieto A, Pamies R, Oliver F, Medina A, Caballero L, Mazon A. Montelukast improves pulmonary function measured by impulse oscillometry in children with asthma (Mio study). Respiratory Medicine. 2006 Jul 1;100(7):1180-5.

Maneechotesuwan K, Sujaritwongsanon P, Suthamsmai T. IgE production in allergic asthmatic patients with different asthma control status. Journal of the Medical Association of Thailand. 2011 Nov 17;93(1):71.

Kovač K, Dodig S, Tješić-Drinković D, Raos M. Correlation between asthma severity and serum IgE in asthmatic children sensitized to Dermatophagoides pteronyssinus. Archives of medical research. 2007 Jan 1;38(1):99-105.

Borish L, Chipps B, Deniz Y, Gujrathi S, Zheng B, Dolan CM, TENOR Study Group. Total serum IgE levels in a large cohort of patients with severe or difficult-to-treat asthma. Annals of Allergy, Asthma & Immunology. 2005 Sep 1;95(3):247-53.

Qu X, Chen Y, Yin C. Effect of montelukast on the expression of CD4+ CD25+ regulatory T cells in children with acute bronchial asthma. Experimental and Therapeutic Medicine. 2018 Sep 1;16(3):2381-6.

Stelmach I, Bobrowska-Korzeniowska M, Majak P, Stelmach W, Kuna P. The effect of montelukast and different doses of budesonide on IgE serum levels and clinical parameters in children with newly diagnosed asthma. Pulmonary pharmacology & therapeutics. 2005 Oct 1;18(5):374-80.

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Published

2023-12-26

How to Cite

Haider Mohammed, H. ., Abdul-Reda, U. ., Mahmood Abo-Almaali, H. ., & Mahdi Hussien, A. . (2023). Influence of Genetics Polymorphism of OATP2B1Transporter on Montelukast Response in Samples of Asthmatic Children . Journal of Contemporary Medical Sciences, 9(6). https://doi.org/10.22317/jcms.v9i6.1449