The relationship between IL-4 polymorphisms and asthma: a systematic review
PDF

Keywords

Polymorphisms
Interleukin-4
Asthma

How to Cite

1.
Silva MJA, Monteiro EOL, e Silva BB, Martins DZ da C, Siqueira AS, Santana BB. The relationship between IL-4 polymorphisms and asthma: a systematic review. Rev Inst Adolfo Lutz [Internet]. 2022 Sep. 26 [cited 2024 Jul. 22];81:1-22,e37177. Available from: https://periodicos.saude.sp.gov.br/RIAL/article/view/37177

Abstract

Asthma is a chronic and heterogeneous disease of the airways that begins in childhood and persists, in many cases, into adulthood. The disease is the result of environmental, epigenetic and genetic interactions. This work aims to review the polymorphisms described in the literature in the IL-4 gene associated with susceptibility or protection to the development of asthma. This is a systematic literature review, carried out in PubMed, MEDLINE and Science Direct databases in the time frame from 2000 to July 2021, revealing the following key points: IL-4, Polymorphisms and Asthma. The search resulted in 29 articles, all in English. Despite some divergent studies, the SNP rs2243250, which was the most studied in populations from different countries, was also the one that found the most correlations of susceptibility with the disease. It is concluded that although there is controversial data on IL-4 SNPs related to the disease, the association of pangenomic studies has brought a list of genes and their variations associated with the risk of developing asthma, such as the rs2243250 SNP that was well related in populations of several countries analyzed.

https://doi.org/10.53393/rial.2022.v.81.37177
PDF

References

1. Bousquet J. Global initiative for asthma (GINA) and its objectives. Clin Exp Allergy. 2000;30(Suppl):2-5. https://dx.doi.org/10.1046/j.1365-2222.2000.00088.x

2. Busse WW, Lemanske RF Jr. Asthma. New Engl J Med. 2001;344(5):350-62. https://dx.doi.org/10.1056/NEJM200102013440507

3. Moore WC, Meyers DA, Wenzel SE, Teague WG, Li H, Li X et al. Identification of asthma phenotypes using cluster analysis in the Severe Asthma Research Program. Am J Respir Crit Care Med. 2010;181(4):315-23. https://dx.doi.org/10.1164/rccm.200906-0896OC

4. Hofmann AM, Abraham SN. New roles for mast cells in modulating allergic reactions and immunity against pathogens. Curr Opin Immunol. 2009;21(6):679-86. https://dx.doi.org/10.1016/j.coi.2009.09.007

5. Samitas K, Delimpoura V, Zervas E, Gaga M. Anti-IgE treatment, airway inflammation and remodelling in severe allergic asthma: current knowledge and future perspectives. Eur Respir Rev. 2015;24(138):594-601.

https://dx.doi.org/10.1183/16000617.00001715

6. Nabe T, Wakamori H, Takiguchi A, Kida H, Ohya S, Mizutani N et al. Analyses of IL-33-producing cells during multiple antigen challenges in murine asthma. J Allergy Clin Immunol. 2014;133(2):AB61. https://dx.doi.org/10.1016/j.jaci.2013.12.243

7. Broide DH, Finkelman F, Bochner BS, Rothenberg ME. Advances in mechanisms of asthma, allergy, and immunology in 2010. J Allergy Clin Immunol. 2011;127(3):689-95. https://dx.doi.org/10.1016/j.jaci.2011.01.027

8. Wang TN, Tseng HI, Kao CC, Chu YT, Chen WY, Wu PF et al. The effects of NOS1 gene on asthma and total IgE levels in Taiwanese children, and the interactions with environmental factors. Pediatr Allergy Immunol. 2010;21(7):1064-1071. https://dx.doi.org/10.1111/j.1399-3038.2009.00981.x

9. Todo-Bom A, Pinto AM. Fisiopatologia da asma grave. Rev Port Imunoalergol. 2006;14(Supl 2):43-8.

10. Nadler MJ, Matthews SA, Turner H, Kinet JP. Signal transduction by the high-affinity immunoglobulin E receptor Fc epsilon RI: coupling form to function. Adv Immunol. 2000;76:325-55. https://dx.doi.org/10.1016/s0065-2776(01)76022-1

11. Quirt J, Hildebrand KJ, Mazza J, Noya F, Kim H. Asthma. Allergy Asthma Clin Immunol. 2018;14(Suppl 2):50. https://dx.doi.org/10.1186/s13223-018-0279-0

12. Stark JM, Tibbitt CA, Coquet JM. The metabolic requirements of Th2 cell differentiation. Front Immunol. 2019;10:2318. https://dx.doi.org/10.3389/fimmu.2019.02318

13. Gilmour J, Lavender P. Control of IL-4 expression in T helper 1 and 2 cells. Immunology. 2008;124(4):437-44. https://dx.doi.org/10.1111/j.1365-2567.2008.02845.x

14. Pandey R, Parkash V, Kant S, Verma AK, Sankhwar SN, Agrawal A et al. An update on the diagnostic biomarkers for asthma. J Family Med Prim Care. 2021;10(3):1139-48. https://dx.doi.org/10.4103/jfmpc.jfmpc_2037_20

15. Harms RZ, Borengasser K, Kumar V, Sarvetnick N. Anti-human interleukin(IL)-4 clone 8D4-8 crossreacts with myosin-9 associated with apoptotic cells and should not be used for flow cytometry applications querying IL-4 expression. Front Cell Dev Biol. 2019;7:46. https://dx.doi.org/10.3389/fcell.2019.00046

16. Renauld JC. New insights into the role of cytokines in asthma. J Clin Pathol. 2001;54(8):577-89. https://dx.doi.org/10.1136/jcp.54.8.577

17. Yu K, Lieber MR. Current insights into the mechanism of mammalian immunoglobulin class switch recombination. Crit Rev Biochem Mol Biology. 2019;54(4):333-51. https://dx.doi.org/10.1080/10409238.2019.1659227

18. Fleming L. Asthma exacerbation prediction: recent insights. Curr Opin Allergy Clin Immunol. 2018;18(2):117-23. https://dx.doi.org/10.1097/ACI.0000000000000428

19. Chai R, Liu B, Qi F. The significance of the levels of IL-4, IL-31 and TLSP in patients with asthma and/ or rhinitis. Immunotherapy. 2017;9(4):331-7. https://dx.doi.org/10.2217/imt-2016-0131

20. Li P, Yang QZ, Wang W, Zhang GQ, Yang J. Increased IL-4- and IL-17-producing CD8+ cells are related to decreased CD39+ CD4+ Foxp3+ cells in allergic asthma. J Asthma. 2018;55(1):8-14. https://dx.doi.org/10.1080/02770903.2017.1310225

21. Liu Y, Gao X, Miao Y, Wang Y, Wang H, Cheng Z et al. NLRP3 regulates macrophage M2 polarization through up-regulation of IL-4 in asthma. Biochem J. 2018;475(12):1995-2008. https://dx.doi.org/10.1042/BCJ20180086

22. Ladjemi MZ, Gras D, Dupasquier S, Detry B, Lecocq M, Garulli C et al. Bronchial epithelial IgA secretion is impaired in asthma. Role of IL-4/IL-13. Am J Respir Crit Care Med. 2018;197(11):1396-1409. https://dx.doi.org/10.1164/rccm.201703-0561OC

23. Xia F, Deng C, Jiang Y, Qu Y, Deng J, Cai Z et al. IL4 (interleukin 4) induces autophagy in B cells leading to exacerbated asthma. Autophagy. 2018;14(3):450-64. https://dx.doi.org/10.1080/15548627.2017.1421884

24. Basehore MJ, Howard TD, Lange LA, Moore WC, Hawkins GA, Marshik PL et al. A comprehensive evaluation of IL4 variants in ethnically diverse populations: association of total serum IgE levels and asthma in white subjects. J Allergy Clin Immunol. 2004;114(1):80-7. https://dx.doi.org/10.1016/j.jaci.2004.05.035

25. Thomsen SF. Genetics of asthma: an introduction for the clinician. Eur Clin Respir J. 2015;2:24643. https://dx.doi.org/10.3402/ecrj.v2.24643

26. O’Rielly DD, Rahman P. Genetic epidemiology of complex phenotypes. Methods Mol Biol. 2021;2249:335-67. https://dx.doi.org/10.1007/978-1-0716-1138-8_19

27. Reis LM, Rodrigues FW, Silva RE da, Taleb AC, Ávila MP de. Relation analysis of the occurrence of single nucleotide polymorphism of the DOCK9 gene in keratoconus. Rev Bras Oftalmol. 2016;75:223-27. https://dx.doi.org/10.5935/0034-7280.20160046

28. Rother ET. Revisão sistemática X revisão narrativa. Acta Paul Enferm. 2007;20(2):v-vi. https://dx.doi.org/10.1590/S0103-21002007000200001

29. Santos CMC, Pimenta CAM, Nobre MRC. The PICO strategy for the research question construction and evidence search. Rev Lat Am Enferm. 2007;15(3):508-11. https://dx.doi.org/10.1590/S0104-11692007000300023

30. Aguayo-Albasini JL, Flores-Pastor B, Soria-Aledo V. Sistema GRADE: clasificación de la calidad de la evidencia y graduación de la fuerza de la recomendación. Cir Esp. 2014;92(2):82-8. https://dx.doi.org/10.1016/j.ciresp.2013.08.002

31. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JPA et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700. https://dx.doi.org/10.1136/bmj.b2700

32. Ambrocio-Ortiz E, Galicia-Negrete G, Pérez-Rubio G, Escobar-Morales AJ, Abarca-Rojano E, Del Angel-Pablo AD et al. Single nucleotide and copy-number variants in IL4 and IL13 are not associated with asthma susceptibility or inflammatorymarkers: a case-control study in a Mexican-Mestizo population. Diagnostics (Basel). 2020;10(5):273.

https://dx.doi.org/10.3390/diagnostics10050273

33. Zhang G, Khoo SK, Mäkelä MJ, Candelaria P, Hayden CM, von Hertzen L et al. Maternal genetic variants of IL4/IL13 pathway genes on IgE with “Western or Eastern Environments/Lifestyles”. Allergy Asthma Immunol Res. 2014;6(4):350-6. https://dx.doi.org/10.4168/aair.2014.6.4.350

34. Padrón-Morales J, Sanz C, Dávila I, Muñoz-Bellido F, Lorente F, Isidoro-García M. Polymorphisms of the IL12B, IL1B, and TNFA genes and susceptibility to asthma. J Investig Allergol Clin Immunol. 2013;23(7):487-94.

35. Miyake Y, Tanaka K, Arakawa M. Relationship between polymorphisms in IL4 and asthma in Japanese women: the Kyushu Okinawa Maternal and Child Health Study. J Investig Allergol Clin Immunol. 2013;23(4):242-7.

36. Isidoro-García M, Dávila I, Laffond E, Moreno E, Lorente F, González-Sarmiento R. Interleukin-4 (IL4) and Interleukin-4 receptor (IL4RA) polymorphisms in asthma: a case control study. Clin Mol Allergy. 2005;3:15.

https://dx.doi.org/10.1186/1476-7961-3-15

37. Bai S, Hua L, Wang X, Liu Q, Bao Y. Association of a 4-locus gene model including IL13, IL4, FCER1B, and ADRB2 with the asthma predictive index and atopy in Chinese Han Children. J Investig Allergol Clin Immunol. 2018;28(6):407-13. https://dx.doi.org/10.18176/jiaci.0272

38. Berenguer AG, Fernandes AT, Oliveira S, Rodrigues M, Ornelas P, Romeira D et al. Genetic polymorphisms and asthma: findings from a case-control study in the Madeira island population. Bio Res. 2014;47(1):40. https://dx.doi.org/10.1186/0717-6287-47-40

39. Smolnikova MV, Smirnova SV, Freidin MB, Tyutina OS. Immunological parameters and gene polymorphisms (C-590T IL4, C-597A IL10) in severe bronchial asthma in children from the Krasnoyarsk region, West Siberia. Int J Circumpolar Health. 2013;72. https://dx.doi.org/10.3402/ijch.v72i0.21159

40. Davoodi P, Mahesh PA, Holla AD, Ramachandra NB. A preliminary study on the association of single nucleotide polymorphisms of interleukin 4 (IL4), IL13, IL4 receptor alpha (IL4Rα) & Toll-like receptor 4 (TLR4) genes with asthma in Indian adults. Indian J Med Res. 2015;142(6):675-80. https://dx.doi.org/10.4103/0971-5916.174551

41. Chiang CH, Lin MW, Chung MY, Yang UC. The association between the IL-4, ADRβ2 and ADAM 33 gene polymorphisms and asthma in the Taiwanese population. J Chin Med Assoc. 2012;75(12):635-43. https://dx.doi.org/10.1016/j.jcma.2012.08.012

42. Michel S, Liang L, Depner M, Klopp N, Ruether A, Kumar A et al. Unifying candidate gene and GWAS Approaches in Asthma. PloS One. 2010;5(11):e13894. https://dx.doi.org/10.1371/journal.pone.0013894

43. Li X, Hawkins GA, Moore WC, Hastie AT, Ampleford EJ, Milosevic J et al. Expression of asthma susceptibility genes in bronchial epithelial cells and bronchial alveolar lavage in the Severe Asthma Research Program (SARP) cohort. J Asthma. 2016;53(8):775-82. https://dx.doi.org/10.3109/02770903.2016.1158268

44. Donfack J, Schneider DH, Tan Z, Kurz T, Dubchak I, Frazer KA et al. Variation in conserved noncoding sequences on chromosome 5q and susceptibility to asthma and atopy. Respir Res. 2005;6(1):145. https://dx.doi.org/10.1186/1465-9921-6-145

45. de Guia RM, Ramos JDA. The -590C/TIL4 single-nucleotide polymorphism as a genetic factor of atopic allergy. Int J Mol Epidemiol Genet. 2010;1(1):67-73.

46. Ramphul K, Lv J, Hua L, Liu QH, Fang DZ, Ji RX et al. Single nucleotide polymorphisms predisposing to asthma in children of Mauritian Indian and Chinese Han ethnicity. Braz J Med Biol Res. 2014;47(5):394-7. https://dx.doi.org/10.1590/1414-431X20143751

47. Yang XX, Li FX, Wu YS, Wu D, Tan JY, Li M. Association of TGF-beta1, IL-4 and IL-13 gene polymerphisms with asthma in a Chinese population. Asian Pac J Allergy Immunol. 2011;29(3):273-7.

48. Li H, Xiaoyan D, Quanhua L, Jie L, Yixiao B. Single-nucleotide polymorphisms in genes predisposing to asthma in children of Chinese Han nationality. J Investig Allergol Clin Immunol. 2009;19(5):391-5.

49. Battle NC, Choudhry S, Tsai HJ, Eng C, Kumar G, Beckman KB et al. Ethnicity-specific gene-gene interaction between IL-13 and IL-4Ralpha among African Americans with asthma. Am J Respir Crit Care Med. 2007;175(9):881-7.

https://dx.doi.org/10.1164/rccm.200607-992OC

50. Hua L, Liu Q, Li J, Zuo X, Chen Q, Li J et al. Gene-gene and gene-environment interactions on cord blood total IgE in Chinese Han children. Allergy Asthma Clin Immunol. 2021;17(1):69. https://dx.doi.org/10.1186/s13223-021-00571-0

51. Haller G, Torgerson DG, Ober C, Thompson EE. Sequencing the IL4 locus in African Americans implicates rare noncoding variants in asthma susceptibility. J Allergy Clin Immunol. 2009;124(6):1204-9.e9. https://dx.doi.org/10.1016/j.jaci.2009.09.013

52. Ramphul K, Hua L, Bao YX, Li JY, Liu QH, Ji RX et al. Identification of IL13 C1923T as a single nucleotide polymorphism for asthma in children from Mauritius. Pediatr Allergy Immunol Pulmonol. 2015;28(2):92-5. https://dx.doi.org/10.1089/ped.2014.0464

53. Ricciardolo FL, Sorbello V, Silvestri M, Giacomelli M, Debenedetti VM, Malerba M et al. TNFalpha, IL-4R-alpha and IL-4 polymorphisms in mild to severe asthma from Italian Caucasians. Int J Immunopathol Pharmacol. 2013;26(1):75-84. https://dx.doi.org/10.1177/039463201302600107

54. Baye TM, Butsch Kovacic M, Biagini Myers JM, Martin LJ, Lindsey M, Patterson TL et al. Differences in candidate gene association between European ancestry and African American asthmatic children. PLoS One. 2011;6(2):e16522.

https://dx.doi.org/10.1371/journal.pone.0016522

55. Hussein IA, Jaber SH. Genotyping of IL-4 -590 (C>T) gene in Iraqi asthma patients. Dis Markers. 2017;2017:5806236. https://dx.doi.org/10.1155/2017/5806236

56. Dmitrieva-Zdorova EV, Voronko OE, Latysheva EA, Storozhakov GI, Archakov AI. Analysis of polymorphisms in T(H)2-associated genes in Russian patients with atopic bronchial asthma. J Investig Allergol Clin Immunol. 2012;22(2):126-32.

57. Hur GY, Ye YM, Koh DH, Kim SH, Park HS. IL-4 receptor α polymorphisms may be a susceptible factor for work-related respiratory symptoms in Bakery workers. Allergy Asthma Immunol Res. 2013;5(6):371-6. https://dx.doi.org/10.4168/aair.2013.5.6.371

58. Micheal S, Minhas K, Ishaque M, Ahmed F, Ahmed A. IL-4 gene polymorphisms and their association with atopic asthma and allergic rhinitis in Pakistani patients. J Investig Allergol Clin Immunol. 2013;23(2):107-11.

59. Beghé B, Barton S, Rorke S, Peng Q, Sayers I, Gaunt T et al. Polymorphisms in the interleukin-4 and interleukin-4 receptor alpha chain genes confer susceptibility to asthma and atopy in a Caucasian population. Clin Exp Allergy. 2003;33(8):1111-7. https://dx.doi.org/10.1046/j.1365-2222.2003.01731.x

60. Klaassen EM, Penders J, Jöbsis Q, van de Kant KD, Thijs C, Mommers M et al. An ADAM33 polymorphism associates with progression of preschool wheeze into childhood asthma: a prospective case-control study with replication in a birth cohort study. PLoS One. 2015;10(3):e0119349. https://dx.doi.org/10.1371/journal.pone.0119349

61. Ferwerda B, McCall MB, Verheijen K, Kullberg BJ, van der Ven AJ, Van der Meer JW et al. Functional consequences of toll-like receptor 4 polymorphisms. Mol Med. 2008;14(5–6):346-52. https://dx.doi.org/10.2119/2007-00135.Ferwerda

62. Doetschman T. Influence of genetic background on genetically engineered mouse phenotypes. Methods Mol Biol. 2009;530:423-33. https://dx.doi.org/10.1007/978-1-59745-471-1_23

63. Johnson KR, Zheng QY, Noben-Trauth K. Strain background effects and genetic modifiers of hearing in mice. Brain Res. 2006;1091(1):79-88. https://dx.doi.org/10.1016/j.brainres.2006.02.021

64. Sigmund CD. Viewpoint: are studies in genetically altered mice out of control? Arterioscler Thromb Vasc Biol. 2000;20(6):1425-9. https://dx.doi.org/10.1161/01.ATV.20.6.1425

65. Padrón-Morales J, García-Solaesa V, Isidoro-García M, Hernández-Hernández L, García-Sánchez A, Hincapié-López G et al. Implications of cytokine genes in allergic asthma. Allergol Immunopathol (Madr). 2014;42(6):603-8.

https://dx.doi.org/10.1016/j.aller.2013.11.006

66. Imani D, Eslami MM, Anani-Sarab G, Aliyu M, Razi B, Rezaei R. Interleukin-4 gene polymorphism (C33T) and the risk of the asthma: a meta-analysis based on 24 publications. BMC Med Genet. 2020;21(1):232. https://dx.doi.org/10.1186/s12881-020-01169-w

67. Kousha A, Mahdavi Gorabi A, Forouzesh M, Hosseini M, Alexander M, Imani D et al. Interleukin 4 gene polymorphism (-589C/T) and the risk of asthma: a meta-analysis and met-regression based on 55 studies. BMC Immunol. 2020;21(1):55. https://dx.doi.org/10.1186/s12865-020-00384-7

68. Mukherjee S, Huda S, Sinha Babu SP. Toll-like receptor polymorphism in host immune response to infectious diseases: a review. Scand J Immunol. 2019;90(1):e12771. https://dx.doi.org/10.1111/sji.12771

69. Vercelli D. Discovering susceptibility genes for asthma and allergy. Nat Rev Immunol. 2008;8(3):169-82. https://dx.doi.org/10.1038/nri2257

70. Hassan M, Jo T, Risse PA, Tolloczko B, Lemière C, Olivenstein R et al. Airway smooth muscle remodeling is a dynamic process in severe long-standing asthma. J Allergy Clin Immunol. 2010;125(5):1037-1045.e3. https://dx.doi.org/10.1016/j.jaci.2010.02.031

71. Kirstein F, Horsnell WG, Kuperman DA, Huang X, Erle DJ, Lopata AL et al. Expression of IL-4 receptor alpha on smooth muscle cells is not necessary for development of experimental allergic asthma. J Allergy Clin Immunol. 2010;126(2):347-54. https://dx.doi.org/10.1016/j.jaci.2010.04.028

72. Tachdjian R, Al Khatib S, Schwinglshackl A, Kim HS, Chen A, Blasioli J et al. In vivo regulation of the allergic response by the IL-4 receptor alpha chain immunoreceptor tyrosine-based inhibitory motif. J Allergy Clin Immunol. 2010;125(5):1128-1136.e8. https://dx.doi.org/10.1016/j.jaci.2010.01.054

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Copyright (c) 2022 Instituto Adolfo Lutz Journal

Downloads

Download data is not yet available.