Polymorphisms of 444A > C Leukotriene C4 Synthase (LTC4S) in Asthmatic Iraqi Patients
Keywords:
Asthma, 444A > C, LTC4S, rs730012
Abstract
The aim of this study was to investigate the association of the LTC4S rs730012 C/A polymorphism with asthma susceptibility in Iraqi patients. Forty-five asthmatic patients and 35 healthy controls were genotyped for the rs730012 C/A gene polymorphism. The distribution frequencies of genotypes and alleles of the rs730012 gene were in Hardy-Weinberg equilibrium in both patients and control groups. The most common genotype in both control and asthma patients was the heterozygous genotype CA with a percentage of 80% and 57.78% respectively. The genotype CC was higher in the asthmatic group (40%) compared to the control group (11.43%). In contrast, genotype AA, the less predominant genotype, was less in the asthmatic group were less in asthmatic group (2.22%) compared control group (8.57%). The C allele was more predominant compared to the A allele with percentages of 51.43% and 68.89% for C, 48.57% and 31.11% for A in the control and patient groups respectively with significant differences (p =0.02451). The association analysis displayed that the individuals carrying the homozygous CC genotype were more likely to have a significantly increased risk of asthma with OR=5.1667 (Cl95%1.5562 to 17.1541) (p= 0.0073). The heterozygous CA and homozygous AA genotypes decrease the association with asthma OR=0.3421 (CI95%0.1236 to 0.9467) and OR=0.2424 (CI95%0.0241 to 2.4388) respectively. However, the difference between the control and asthma groups of the CA genotype was significant (p=0.0389) but not for the AA genotype (P=0.2289). These results suggested that the C allele might play a risk factor for asthma whereas the A allele might consider a protective role against asthma.
References
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27. Drazen JM, O'Brien J, Sparrow D, Weiss ST, Martins MA, Israel E, et al. Recovery of Leukotriene E4 from the Urine of Patients. Am Rev Respir Dis. 1992;148:104-8.
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30. Cowburn AS, Sladek K, Soja J, Adamek L, Nizankowska E, Szczeklik A, et al. Overexpression of leukotriene C4 synthase in bronchial biopsies from patients with aspirin-intolerant asthma. The Journal of clinical investigation. 1998;101(4):834-46.
31. Penrose JF, Spector J, Baldasaro M, Xu K, Boyce J, Arm JP, et al. Molecular Cloning of the Gene for Human Leukotriene C4 Synthase: ORGANIZATION, NUCLEOTIDE SEQUENCE, AND CHROMOSOMAL LOCALIZATION TO 5q35 (∗). Journal of Biological Chemistry. 1996;271(19):11356-61.
32. Hsieh FH, Lam BK, Penrose JF, Austen KF, Boyce JA. T Helper Cell Type 2 Cytokines Coordinately Regulate Immunoglobulin E–dependent Cysteinyl Leukotriene Production by Human Cord Blood–derived Mast Cells: Profound Induction of Leukotriene C4 Synthase Expression by Interleukin 4. The Journal of Experimental Medicine. 2001;193(1):123-34.
33. Rosenwasser LJ, Boyce JA. Mast cells: beyond IgE. Journal of Allergy and Clinical Immunology. 2003;111(1):24-32.
2. Hammad H, Lambrecht BN. The basic immunology of asthma. Cell. 2021;184(6):1469-85.
3. Ferreira MA, Vonk JM, Baurecht H, Marenholz I, Tian C, Hoffman JD, et al. Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology. Nature genetics. 2017;49(12):1752-7.
4. Makoui MH, Imani D, Motallebnezhad M, Azimi M, Razi B. Vitamin D receptor gene polymorphism and susceptibility to asthma: meta-analysis based on 17 case-control studies. Annals of Allergy, Asthma & Immunology. 2020;124(1):57-69.
5. Rogers AJ, Raby BA, Lasky-Su JA, Murphy A, Lazarus R, Klanderman BJ, et al. Assessing the reproducibility of asthma candidate gene associations, using genome-wide data. American journal of respiratory and critical care medicine. 2009;179(12):1084-90.
6. March ME, Sleiman PMA, Hakonarson H. Genetic polymorphisms and associated susceptibility to asthma. International journal of general medicine. 2013:253-65.
7. Hay DWP, Torphy TJ, Undem BJ. Cysteinyl leukotrienes in asthma: old mediators up to new tricks. Trends in pharmacological sciences. 1995;16(9):304-9.
8. Lam BK. Leukotriene C4 synthase: a critical enzyme for the biosynthesis of SRS-A. Front Biosci. 1997;2:d380-d6.
9. Lam BK, Penrose JF, Freeman GJ, Austen KF. Expression cloning of a cDNA for human leukotriene C4 synthase, an integral membrane protein conjugating reduced glutathione to leukotriene A4. Proceedings of the National Academy of Sciences. 1994;91(16):7663-7.
10. Lam BK, Owen WF, Austen KF, Soberman RJ. The identification of a distinct export step following the biosynthesis of leukotriene C4 by human eosinophils. Journal of Biological Chemistry. 1989;264(22):12885-9.
11. Lam BK, Wong PY. Phospholipase A2 (PLA2) release leukotrienes and other lipoxygenase products from endogenous sources. Advances in prostaglandin, thromboxane, and leukotriene research. 1989;19:598-601.
12. Anderson ME, Allison RD, Meister A. Interconversion of leukotrienes catalyzed by purified gamma-glutamyl transpeptidase: concomitant formation of leukotriene D4 and gamma-glutamyl amino acids. Proceedings of the National Academy of Sciences. 1982;79(4):1088-91.
13. Lee CW, Lewis RA, Corey EJ, Austen KF. Conversion of leukotriene D4 to leukotriene E4 by a dipeptidase released from the specific granule of human polymorphonuclear leucocytes. Immunology. 1983;48(1):27.
14. Sanak M, Levy BD, Clish CB, Chiang N, Gronert K, Mastalerz L, et al. Aspirin-tolerant asthmatics generate more lipoxins than aspirin-intolerant asthmatics. European Respiratory Journal. 2000;16(1):44-9.
15. Hui Y, Funk CD. Cysteinyl leukotriene receptors. Biochemical pharmacology. 2002;64(11):1549-57.
16. Henderson WR. The role of leukotrienes in inflammation. Annals of internal medicine. 1994;121(9):684-97.
17. Henderson Jr WR. Role of leukotrienes in asthma. Annals of allergy. 1994;72(3):272-8.
18. Arriba-Méndez S, Sanz C, Isidoro-García M, Pascual M, Avila C, Dávila I, et al. Analysis of 927T> C CYSLTR1 and–444A> C LTC4S polymorphisms in children with asthma. Allergologia et immunopathologia. 2008;36(5):259-63.
19. Freidin MB, Puzyrev VP. Syntropic genes of allergic diseases. Russian journal of genetics. 2010;46:224-9.
20. Jiad LA, Ahmed IH. Investigation Of The Molecular Role Of Cell-Free Nuclear DNA And Cell-Free Mitochondrial DNA In Asthmatic Patients. NVEO-NATURAL VOLATILES & ESSENTIAL OILS Journal| NVEO. 2022:450-5.
21. Berghea EC, Popa LO, Dutescu MI, Meirosu M, Farcasanu IC, Berghea F, et al. Association of leukotriene C4 synthase A-444C polymorphism with asthma and asthma phenotypes in Romanian population. Maedica. 2015;10(2):91.
22. Kmyta V, Cherednichenko N, Prystupa L. -444 A/C polymorphism in the leukotriene-C4 synthase gene in patients with bronchial asthma. Eur Respiratory Soc; 2018.
23. Zhang Y, Huang H, Huang J, Xiang Z, Yang M, Tian C, et al. The −444A/C Polymorphism in the LTC4S Gene and the Risk of Asthma: A Meta-analysis. Archives of Medical Research. 2012;43(6):444-50.
24. Ferreri NR, Howland WC, Stevenson DD, Spiegelberg HL. Release of leukotrienes, prostaglandins, and histamine into nasal secretions of aspirin-sensitive asthmatics during reaction to aspirin. American Review of Respiratory Disease. 1988;137(4):847-54.
25. Lam S, Chan H, LeRiche JC, Chan-Yeung M, Salari H. Release of leukotrienes in patients with bronchial asthma. Journal of allergy and clinical immunology. 1988;81(4):711-7.
26. Wenzel SE, Larsen GL, Johnston K, Voelkel NF, Westcott JY. Elevated levels of leukotriene C4 in bronchoalveolar lavage fluid from atopic asthmatics after endobronchial allergen challenge. Am Rev Respir Dis. 1990;142(1):112-9.
27. Drazen JM, O'Brien J, Sparrow D, Weiss ST, Martins MA, Israel E, et al. Recovery of Leukotriene E4 from the Urine of Patients. Am Rev Respir Dis. 1992;148:104-8.
28. Sanak M, Simon H-U, Szczeklik A. Leukotriene C4 synthase promoter polymorphism and risk of aspirin-induced asthma. Lancet. 1997;350(9091):1599-.
29. Sanak M, Pierzchalska M, Bazan-Socha S, Szczeklik A. Enhanced expression of the leukotriene C4 synthase due to overactive transcription of an allelic variant associated with aspirin-intolerant asthma. American Journal of Respiratory Cell and Molecular Biology. 2000;23(3):290-6.
30. Cowburn AS, Sladek K, Soja J, Adamek L, Nizankowska E, Szczeklik A, et al. Overexpression of leukotriene C4 synthase in bronchial biopsies from patients with aspirin-intolerant asthma. The Journal of clinical investigation. 1998;101(4):834-46.
31. Penrose JF, Spector J, Baldasaro M, Xu K, Boyce J, Arm JP, et al. Molecular Cloning of the Gene for Human Leukotriene C4 Synthase: ORGANIZATION, NUCLEOTIDE SEQUENCE, AND CHROMOSOMAL LOCALIZATION TO 5q35 (∗). Journal of Biological Chemistry. 1996;271(19):11356-61.
32. Hsieh FH, Lam BK, Penrose JF, Austen KF, Boyce JA. T Helper Cell Type 2 Cytokines Coordinately Regulate Immunoglobulin E–dependent Cysteinyl Leukotriene Production by Human Cord Blood–derived Mast Cells: Profound Induction of Leukotriene C4 Synthase Expression by Interleukin 4. The Journal of Experimental Medicine. 2001;193(1):123-34.
33. Rosenwasser LJ, Boyce JA. Mast cells: beyond IgE. Journal of Allergy and Clinical Immunology. 2003;111(1):24-32.
Published
2023-08-30
How to Cite
Masar Abd Manaf Abdulmutaleb, & Dr. Intisar Hussein Ahmed. (2023). Polymorphisms of 444A > C Leukotriene C4 Synthase (LTC4S) in Asthmatic Iraqi Patients. Central Asian Journal of Medical and Natural Science, 4(4), 659-666. Retrieved from https://cajmns.centralasianstudies.org/index.php/CAJMNS/article/view/1769
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