Tuberculosis and Respiratory Diseases

The Korean Academy of Tuberculosis and Respiratory Diseases (대한결핵및호흡기학회)
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Epigenetic Changes in Asthma: Role of DNA CpG Methylation

  • Bae, Da-Jeong (Department of Interdisciplinary Program in Biomedical Science Major, Soonchunhyang Graduate School) ;
  • Jun, Ji Ae (Department of Interdisciplinary Program in Biomedical Science Major, Soonchunhyang Graduate School) ;
  • Chang, Hun Soo (Department of Environmental Health Sciences, Soonchunhyang University) ;
  • Park, Jong Sook (Division of Allergy and Respiratory Medicine, Genome Research Center, Soonchunhyang University Bucheon Hospital) ;
  • Park, Choon-Sik (Division of Allergy and Respiratory Medicine, Genome Research Center, Soonchunhyang University Bucheon Hospital)
  • Received : 2018.12.26
  • Accepted : 2019.08.30
  • Published : 2020.01.31
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Abstract

For the past three decades, more than a thousand of genetic studies have been performed to find out the genetic variants responsible for the risk of asthma. Until now, all of the discovered single nucleotide polymorphisms have explained genetic effects less than initially expected. Thus, clarification of environmental factors has been brought up to overcome the 'missing' heritability. The most exciting solution is epigenesis because it intervenes at the junction between the genome and the environment. Epigenesis is an alteration of genetic expression without changes of DNA sequence caused by environmental factors such as nutrients, allergens, cigarette smoke, air pollutants, use of drugs and infectious agents during pre- and post-natal periods and even in adulthood. Three major forms of epigenesis are composed of DNA methylation, histone modifications, and specific microRNA. Recently, several studies have been published on epigenesis in asthma and allergy as a powerful tool for research of genetic heritability in asthma albeit epigenetic changes are at the starting point to obtain the data on specific phenotypes of asthma. In this presentation, we mainly review the potential role of DNA CpG methylation in the risk of asthma and its sub-phenotypes including nonsteroidal anti-inflammatory exacerbated respiratory diseases.

Keywords

References

  1. Edfors-Lubs ML. Allergy in 7000 twin pairs. Acta Allergol 1971;26:249-85. https://doi.org/10.1111/j.1398-9995.1971.tb01300.x
  2. Moffatt MF, Kabesch M, Liang L, Dixon AL, Strachan D, Heath S, et al. Genetic variants regulating ORMDL3 expression contribute to the risk of childhood asthma. Nature 2007;448:470-3. https://doi.org/10.1038/nature06014
  3. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, et al. Finding the missing heritability of complex diseases. Nature 2009;461:747-53. https://doi.org/10.1038/nature08494
  4. Vercelli D. Learning from discrepancies: CD14 polymorphisms, atopy and the endotoxin switch. Clin Exp Allergy 2003;33:153-5. https://doi.org/10.1046/j.1365-2222.2003.01606.x
  5. Bouzigon E, Corda E, Aschard H, Dizier MH, Boland A, Bousquet J, et al. Effect of 17q21 variants and smoking exposure in early-onset asthma. N Engl J Med 2008;359:1985-94. https://doi.org/10.1056/NEJMoa0806604
  6. Kim SH, Cho BY, Park CS, Shin ES, Cho EY, Yang EM, et al. Alpha-T-catenin (CTNNA3) gene was identified as a risk variant for toluene diisocyanate-induced asthma by genomewide association analysis. Clin Exp Allergy 2009;39:203-12. https://doi.org/10.1111/j.1365-2222.2008.03117.x
  7. Park SM, Park JS, Park HS, Park CS. Unraveling the genetic basis of aspirin hypersensitivity in asthma beyond arachidonate pathways. Allergy Asthma Immunol Res 2013;5:258-76. https://doi.org/10.4168/aair.2013.5.5.258
  8. Park BL, Kim TH, Kim JH, Bae JS, Pasaje CF, Cheong HS, et al. Genome-wide association study of aspirin-exacerbated respiratory disease in a Korean population. Hum Genet 2013;132:313-21. https://doi.org/10.1007/s00439-012-1247-2
  9. Ezkurdia I, Juan D, Rodriguez JM, Frankish A, Diekhans M, Harrow J, et al. Multiple evidence strands suggest that there may be as few as 19,000 human protein-coding genes. Hum Mol Genet 2014;23:5866-78. https://doi.org/10.1093/hmg/ddu309
  10. ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature 2012;489:57-74. https://doi.org/10.1038/nature11247
  11. Demenais F, Margaritte-Jeannin P, Barnes KC, Cookson WOC, Altmuller J, Ang W, et al. Multiancestry association study identifies new asthma risk loci that colocalize with immunecell enhancer marks. Nat Genet 2018;50:42-53. https://doi.org/10.1038/s41588-017-0014-7
  12. Ho SM. Environmental epigenetics of asthma: an update. J Allergy Clin Immunol 2010;126:453-65. https://doi.org/10.1016/j.jaci.2010.07.030
  13. Ptashne M. On the use of the word 'epigenetic'. Curr Biol 2007;17:R233-6. https://doi.org/10.1016/j.cub.2007.02.030
  14. Stevens M, Cheng JB, Li D, Xie M, Hong C, Maire CL, et al. Estimating absolute methylation levels at single-CpG resolution from methylation enrichment and restriction enzyme sequencing methods. Genome Res 2013;23:1541-53. https://doi.org/10.1101/gr.152231.112
  15. Gallo RL. Human skin is the largest epithelial surface for interaction with microbes. J Invest Dermatol 2017;137:1213-4. https://doi.org/10.1016/j.jid.2016.11.045
  16. Um SW, Kim Y, Lee BB, Kim D, Lee KJ, Kim HK, et al. Genome-wide analysis of DNA methylation in bronchial washings. Clin Epigenetics 2018;10:65. https://doi.org/10.1186/s13148-018-0498-8
  17. Belinsky SA, Palmisano WA, Gilliland FD, Crooks LA, Divine KK, Winters SA, et al. Aberrant promoter methylation in bronchial epithelium and sputum from current and former smokers. Cancer Res 2002;62:2370-7.
  18. Breton CV, Byun HM, Wang X, Salam MT, Siegmund K, Gilliland FD. DNA methylation in the arginase-nitric oxide synthase pathway is associated with exhaled nitric oxide in children with asthma. Am J Respir Crit Care Med 2011;184:191-7. https://doi.org/10.1164/rccm.201012-2029OC
  19. Baccarelli A, Rusconi F, Bollati V, Catelan D, Accetta G, Hou L, et al. Nasal cell DNA methylation, inflammation, lung function and wheezing in children with asthma. Epigenomics 2012;4:91-100. https://doi.org/10.2217/epi.11.106
  20. Yang Y, Haitchi HM, Cakebread J, Sammut D, Harvey A, Powell RM, et al. Epigenetic mechanisms silence a disintegrin and metalloprotease 33 expression in bronchial epithelial cells. J Allergy Clin Immunol 2008;121:1393-9. https://doi.org/10.1016/j.jaci.2008.02.031
  21. Tripathi P, Awasthi S, Gao P. ADAM metallopeptidase domain 33 (ADAM33): a promising target for asthma. Mediators Inflamm 2014;2014:572025.
  22. Stefanowicz D, Hackett TL, Garmaroudi FS, Gunther OP, Neumann S, Sutanto EN, et al. DNA methylation profiles of airway epithelial cells and PBMCs from healthy, atopic and asthmatic children. PLoS One 2012;7:e44213. https://doi.org/10.1371/journal.pone.0044213
  23. Kim YJ, Park SW, Kim TH, Park JS, Cheong HS, Shin HD, et al. Genome-wide methylation profiling of the bronchial mucosa of asthmatics: relationship to atopy. BMC Med Genet 2013;14:39.
  24. Breton CV, Byun HM, Wenten M, Pan F, Yang A, Gilliland FD. Prenatal tobacco smoke exposure affects global and gene-specific DNA methylation. Am J Respir Crit Care Med 2009;180:462-7. https://doi.org/10.1164/rccm.200901-0135OC
  25. Foster AM, Baliwag J, Chen CS, Guzman AM, Stoll SW, Gudjonsson JE, et al. IL-36 promotes myeloid cell infiltration, activation, and inflammatory activity in skin. J Immunol 2014;192:6053-61. https://doi.org/10.4049/jimmunol.1301481
  26. Collawn JF, Matalon S. CFTR and lung homeostasis. Am J Physiol Lung Cell Mol Physiol 2014;307:L917-23. https://doi.org/10.1152/ajplung.00326.2014
  27. Santarlasci V, Cosmi L, Maggi L, Liotta F, Annunziato F. IL-1 and T helper immune responses. Front Immunol 2013;4:182. https://doi.org/10.3389/fimmu.2013.00182
  28. White GP, Hollams EM, Yerkovich ST, Bosco A, Holt BJ, Bassami MR, et al. CpG methylation patterns in the IFNgamma promoter in naive T cells: variations during Th1 and Th2 differentiation and between atopics and non-atopics. Pediatr Allergy Immunol 2006;17:557-64. https://doi.org/10.1111/j.1399-3038.2006.00465.x
  29. Shang Y, Das S, Rabold R, Sham JS, Mitzner W, Tang WY. Epigenetic alterations by DNA methylation in house dust miteinduced airway hyperresponsiveness. Am J Respir Cell Mol Biol 2013;49:279-87. https://doi.org/10.1165/rcmb.2012-0403OC
  30. Lluis A, Depner M, Gaugler B, Saas P, Casaca VI, Raedler D, et al. Increased regulatory T-cell numbers are associated with farm milk exposure and lower atopic sensitization and asthma in childhood. J Allergy Clin Immunol 2014;133:551-9. https://doi.org/10.1016/j.jaci.2013.06.034
  31. Perera F, Tang WY, Herbstman J, Tang D, Levin L, Miller R, et al. Relation of DNA methylation of 5'-CpG island of ACSL3 to transplacental exposure to airborne polycyclic aromatic hydrocarbons and childhood asthma. PLoS One 2009;4:e4488. https://doi.org/10.1371/journal.pone.0004488
  32. Breton CV, Siegmund KD, Joubert BR, Wang X, Qui W, Carey V, et al. Prenatal tobacco smoke exposure is associated with childhood DNA CpG methylation. PLoS One 2014;9:e99716. https://doi.org/10.1371/journal.pone.0099716
  33. Yang IV, Pedersen BS, Liu A, O'Connor GT, Teach SJ, Kattan M, et al. DNA methylation and childhood asthma in the inner city. J Allergy Clin Immunol 2015;136:69-80. https://doi.org/10.1016/j.jaci.2015.01.025
  34. Yang IV, Lozupone CA, Schwartz DA. The environment, epigenome, and asthma. J Allergy Clin Immunol 2017;140:14-23. https://doi.org/10.1016/j.jaci.2017.05.011
  35. Rastogi D, Suzuki M, Greally JM. Differential epigenome-wide DNA methylation patterns in childhood obesity-associated asthma. Sci Rep 2013;3:2164. https://doi.org/10.1038/srep02164
  36. Kwon NH, Kim JS, Lee JY, Oh MJ, Choi DC. DNA methylation and the expression of IL-4 and IFN-gamma promoter genes in patients with bronchial asthma. J Clin Immunol 2008;28:139-46. https://doi.org/10.1007/s10875-007-9148-1
  37. Baccarelli A, Wright RO, Bollati V, Tarantini L, Litonjua AA, Suh HH, et al. Rapid DNA methylation changes after exposure to traffic particles. Am J Respir Crit Care Med 2009;179:572-8. https://doi.org/10.1164/rccm.200807-1097OC
  38. Nadeau K, McDonald-Hyman C, Noth EM, Pratt B, Hammond SK, Balmes J, et al. Ambient air pollution impairs regulatory T-cell function in asthma. J Allergy Clin Immunol 2010;126:845-52. https://doi.org/10.1016/j.jaci.2010.08.008
  39. Baines KJ, Simpson JL, Wood LG, Scott RJ, Fibbens NL, Powell H, et al. Sputum gene expression signature of 6 biomarkers discriminates asthma inflammatory phenotypes. J Allergy Clin Immunol 2014;133:997-1007. https://doi.org/10.1016/j.jaci.2013.12.1091
  40. Morales E, Bustamante M, Vilahur N, Escaramis G, Montfort M, de Cid R, et al. DNA hypomethylation at ALOX12 is associated with persistent wheezing in childhood. Am J Respir Crit Care Med 2012;185:937-43. https://doi.org/10.1164/rccm.201105-0870OC
  41. Grabenhenrich LB, Gough H, Reich A, Eckers N, Zepp F, Nitsche O, et al. Early-life determinants of asthma from birth to age 20 years: a German birth cohort study. J Allergy Clin Immunol 2014;133:979-88. https://doi.org/10.1016/j.jaci.2013.11.035
  42. Lee KW, Pausova Z. Cigarette smoking and DNA methylation. Front Genet 2013;4:132. https://doi.org/10.3389/fgene.2013.00132
  43. Joubert BR, Felix JF, Yousefi P, Bakulski KM, Just AC, Breton C, et al. DNA methylation in newborns and maternal smoking in pregnancy: genome-wide consortium meta-analysis. Am J Hum Genet 2016;98:680-96. https://doi.org/10.1016/j.ajhg.2016.02.019
  44. Yoon D, Kim YJ, Cui WY, Van der Vaart A, Cho YS, Lee JY, et al. Large-scale genome-wide association study of Asian population reveals genetic factors in FRMD4A and other loci influencing smoking initiation and nicotine dependence. Hum Genet 2012;131:1009-21. https://doi.org/10.1007/s00439-011-1102-x
  45. Devereux G, Turner SW, Craig LC, McNeill G, Martindale S, Harbour PJ, et al. Low maternal vitamin E intake during pregnancy is associated with asthma in 5-year-old children. Am J Respir Crit Care Med 2006;174:499-507. https://doi.org/10.1164/rccm.200512-1946OC
  46. Forno E, Wang T, Qi C, Yan Q, Xu CJ, Boutaoui N, et al. DNA methylation in nasal epithelium, atopy, and atopic asthma in children: a genome-wide study. Lancet Respir Med 2019;7:336-46. https://doi.org/10.1016/s2213-2600(18)30466-1
  47. Zhou D, Li Z, Yu D, Wan L, Zhu Y, Lai M, et al. Polymorphisms involving gain or loss of CpG sites are significantly enriched in trait-associated SNPs. Oncotarget 2015;6:39995-40004. https://doi.org/10.18632/oncotarget.5650
  48. Astle WJ, Elding H, Jiang T, Allen D, Ruklisa D, Mann AL, et al. The allelic landscape of human blood cell trait variation and links to common complex disease. Cell 2016;167:1415-29. https://doi.org/10.1016/j.cell.2016.10.042
  49. Murphy TM, Wong CC, Arseneault L, Burrage J, Macdonald R, Hannon E, et al. Methylomic markers of persistent childhood asthma: a longitudinal study of asthma-discordant monozygotic twins. Clin Epigenetics 2015;7:130. https://doi.org/10.1186/s13148-015-0163-4
  50. DeVries A, Wlasiuk G, Miller SJ, Bosco A, Stern DA, Lohman IC, et al. Epigenome-wide analysis links SMAD3 methylation at birth to asthma in children of asthmatic mothers. J Allergy Clin Immunol 2017;140:534-42. https://doi.org/10.1016/j.jaci.2016.10.041
  51. Clifford RL, Jones MJ, MacIsaac JL, McEwen LM, Goodman SJ, Mostafavi S, et al. Inhalation of diesel exhaust and allergen alters human bronchial epithelium DNA methylation. J Allergy Clin Immunol 2017;139:112-21. https://doi.org/10.1016/j.jaci.2016.03.046
  52. Lovinsky-Desir S, Jung KH, Jezioro JR, Torrone DZ, de Planell-Saguer M, Yan B, et al. Physical activity, black carbon exposure, and DNA methylation in the FOXP3 promoter. Clin Epigenetics 2017;9:65. https://doi.org/10.1186/s13148-017-0364-0
  53. Jung KH, Lovinsky-Desir S, Yan B, Torrone D, Lawrence J, Jezioro JR, et al. Effect of personal exposure to black carbon on changes in allergic asthma gene methylation measured 5 days later in urban children: importance of allergic sensitization. Clin Epigenetics 2017;9:61. https://doi.org/10.1186/s13148-017-0361-3
  54. Prunicki M, Stell L, Dinakarpandian D, de Planell-Saguer M, Lucas RW, Hammond SK, et al. Exposure to NO2, CO, and PM2.5 is linked to regional DNA methylation differences in asthma. Clin Epigenetics 2018;10:2. https://doi.org/10.1186/s13148-017-0433-4
  55. Jung KH, Torrone D, Lovinsky-Desir S, Perzanowski M, Bautista J, Jezioro JR, et al. Short-term exposure to PM2.5 and vanadium and changes in asthma gene DNA methylation and lung function decrements among urban children. Respir Res 2017;18:63. https://doi.org/10.1186/s12931-017-0550-9
  56. Yiannakopoulou E. Modulation of lymphangiogenesis: a new target for aspirin and other nonsteroidal anti-inflammatory agents? A systematic review. J Clin Pharmacol 2012;52:1749-54. https://doi.org/10.1177/0091270011431066
  57. Pan MR, Chang HC, Chuang LY, Hung WC. The nonsteroidal anti-inflammatory drug NS398 reactivates SPARC expression via promoter demethylation to attenuate invasiveness of lung cancer cells. Exp Biol Med (Maywood) 2008;233:456-62. https://doi.org/10.3181/0709-RM-257
  58. Tahara T, Shibata T, Nakamura M, Yamashita H, Yoshioka D, Okubo M, et al. Chronic aspirin use suppresses CDH1 methylation in human gastric mucosa. Dig Dis Sci 2010;55:54-9. https://doi.org/10.1007/s10620-008-0701-4
  59. Cheong HS, Park SM, Kim MO, Park JS, Lee JY, Byun JY, et al. Genome-wide methylation profile of nasal polyps: relation to aspirin hypersensitivity in asthmatics. Allergy 2011;66:637-44. https://doi.org/10.1111/j.1398-9995.2010.02514.x
  60. Momparler RL. Pharmacology of 5-Aza-2'-deoxycytidine (decitabine). Semin Hematol 2005;42(3 Suppl 2):S9-16. https://doi.org/10.1053/j.seminhematol.2005.05.002

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