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Pharmacogenetic Study in Asthma

Chapter
Part of the Translational Bioinformatics book series (TRBIO, volume 12)

Abstract

Asthma could be viewed as a complex multifactor genetic disease associated with multiple genes. For clinical asthma patients with similar phenotypes, the same treatment can cause very different reactions. Many studies strongly suggest that genetic factors significantly contribute to the clinical outcomes of interindividual pharmacological treatment. To reveal the genetic differences in drug response and drug behavior, pharmacogenomics was developed and expanded to explain the response of drug treatment with acquisition and inheritance factors through the systematic examination of individual variability gene. The pharmacogenetics goal of asthma is to personalize asthma pharmacotherapy and reduce the asthma burden. The present manuscript discusses the coding sequences or regulatory regions of genes that encode proteins involved in asthma pharmacological responses.

Keywords

Asthma Pharmacogenomics Glucocorticoid β2-adrenergic receptor 

Abbreviation

cAMP

Cyclic adenosine monophosphate

FEV1

Forced expiratory volume within 1 s

IL

interleukin

LABA

Long acting β2-agonist

SABA

Short acting β2-agonist

SNP

Single nucleotide polymorphism

UABA

Ultra long acting beta2-agonist

References

  1. 1.
    Miller CA, Slusher LB, Vesell ES. Polymorphism of theophylline metabolism in man. J Clin Invest. 1985;75:1415–25. [PubMed:4039734]CrossRefGoogle Scholar
  2. 2.
    McCracken JL, Veeranki SP, Ameredes BT, Calhoun WJ, Diagnosis. Management of asthma in adults: a review. JAMA. 2017;318:279–90. [PubMed:28719697]CrossRefGoogle Scholar
  3. 3.
    Collaborators. GBDCRD, global, regional, and national deaths, prevalence, disability-adjusted life years, and years lived with disability for chronic obstructive pulmonary disease and asthma, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet Respir Med. 2017;5:691–706. [PubMed:28822787]CrossRefGoogle Scholar
  4. 4.
    Nelson HS, Weiss ST, Bleecker ER, Yancey SW, Dorinsky PM, SS Group. The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest. 2006;129:15–26. [PubMed:16424409]CrossRefGoogle Scholar
  5. 5.
    Bonini M, Usmani OS. The role of the small airways in the pathophysiology of asthma and chronic obstructive pulmonary disease. Ther Adv Respir Dis. 2015;9:281–93.[PubMed:26037949]CrossRefGoogle Scholar
  6. 6.
    Penn RB, Bond RA, Walker JK. GPCRs and arrestins in airways: implications for asthma. Handb Exp Pharmacol. 2014;219:387–403. [PubMed:24292841]CrossRefGoogle Scholar
  7. 7.
    Sayers I. A tailored approach to asthma management: Arg(16) holds the key? Clin Sci (Lond). 2013;124:517–9.[PubMed:23205695]CrossRefGoogle Scholar
  8. 8.
    Wechsler ME, et al. Anticholinergic vs long-acting beta-agonist in combination with inhaled corticosteroids in black adults with asthma: the BELT randomized clinical trial. JAMA. 2015;314:1720–30. [PubMed:26505596]CrossRefGoogle Scholar
  9. 9.
    Ortega VE, et al. Effect of rare variants in ADRB2 on risk of severe exacerbations and symptom control during longacting beta agonist treatment in a multiethnic asthma population: a genetic study. Lancet Respir Med. 2014;2:204–13. [PubMed:24621682]CrossRefGoogle Scholar
  10. 10.
    Litonjua AA. The significance of beta2-adrenergic receptor polymorphisms in asthma. Curr Opin Pulm Med. 2006;12:12–7. [PubMed:16357573]CrossRefGoogle Scholar
  11. 11.
    Thomsen M, Nordestgaard BG, Sethi AA, Tybjaerg-Hansen A, Dahl M. beta2-adrenergic receptor polymorphisms, asthma and COPD: two large population-based studies. Eur Respir J. 2012;39:558–66. [PubMed:22075484]CrossRefGoogle Scholar
  12. 12.
    Bandaru S, Alvala M, Akka J, Sagurthi SR, Nayarisseri A, Singh SK, Mundluru HP. Identification of small molecule as a high affinity β2 agonist promiscuously targeting wild and mutated (Thr164Ile) β 2 adrenergic receptor in the treatment of bronchial asthma. Curr Pharm Des. 2016;22:5221–33. [PubMed:27174812]CrossRefGoogle Scholar
  13. 13.
    Hansen S, Strom M, Maslova E, EL Mortensen CG, SF Olsen A. comparison of three methods to measure asthma in epidemiologic studies: results from the Danish National Birth Cohort. PLoS One. 2012;7:e36328. [PubMed:22606255]CrossRefGoogle Scholar
  14. 14.
    Liang SQ, Chen XL, Deng JM, Wei X, Gong C, ZR Chen ZB. Wang, Beta-2 adrenergic receptor (ADRB2) gene polymorphisms and the risk of asthma: a meta-analysis of case-control studies. PLoS One. 2014;9:e104488. [PubMed:25111792]CrossRefGoogle Scholar
  15. 15.
    Ortega VE. Pharmacogenetics of beta2 adrenergic receptor agonists in asthma management. Clin Genet. 2014;86:12–20. [PubMed:24641588]CrossRefGoogle Scholar
  16. 16.
    Hall IP, Blakey JD, Al Balushi KA, Wheatley A, Sayers I, Pembrey ME, Ring SM, McArdle WL, Strachan DP. Beta2-adrenoceptor polymorphisms and asthma from childhood to middle age in the British 1958 birth cohort: a genetic association study. Lancet. 2006;368:771–9. [PubMed:16935688]CrossRefGoogle Scholar
  17. 17.
    Salam MT, Islam T, Gauderman WJ, Gilliland FD. Roles of arginase variants, atopy, and ozone in childhood asthma. J Allergy Clin Immunol. 2009;123:596–602. 602 e1–8.[PubMed:19281908]CrossRefGoogle Scholar
  18. 18.
    Honkoop PJ, Pinnock H, Kievits-Smeets RM, Sterk PJ, PN Dekhuijzen JC. In ‘t Veen, Adaptation of a difficult-to-manage asthma programme for implementation in the Dutch context: a modified e-Delphi. NPJ Prim Care Respir Med. 2017;27:16086. [PubMed:28184039]CrossRefGoogle Scholar
  19. 19.
    Bouzigon E, et al. Associations between nitric oxide synthase genes and exhaled NO-related phenotypes according to asthma status. PLoS One. 2012;7:e36672. [PubMed:22590587]CrossRefGoogle Scholar
  20. 20.
    Himes BE, et al. Genome-wide association analysis in asthma subjects identifies SPATS2L as a novel bronchodilator response gene. PLoS Genet. 2012;8:e1002824. [PubMed:22792082]CrossRefGoogle Scholar
  21. 21.
    York TP, Vargas-Irwin C, WH Anderson EJ v d O. Asthma pharmacogenetic study using finite mixture models to handle drug-response heterogeneity. Pharmacogenomics. 2009;10:753–67. [PubMed:19450127]CrossRefGoogle Scholar
  22. 22.
    Tantisira KG, Small KM, Litonjua AA, Weiss ST, Liggett SB. Molecular properties and pharmacogenetics of a polymorphism of adenylyl cyclase type 9 in asthma: interaction between beta-agonist and corticosteroid pathways. Hum Mol Genet. 2005;14:1671–7. [PubMed:15879435]CrossRefGoogle Scholar
  23. 23.
    Davenport KL, Huang CH, Davenport MP, Davenport PW. Relationship between respiratory load perception and perception of nonrespiratory sensory modalities in subjects with life-threatening asthma. Pulm Med. 2012;2012:310672. [PubMed:22745905]CrossRefGoogle Scholar
  24. 24.
    Helms PJ. Corticosteroid-sparing options in the treatment of childhood asthma. Drugs. 2000;59 Suppl 1:15–22. discussion 43–5.[PubMed:10741878]CrossRefGoogle Scholar
  25. 25.
    Spahn JD, Szefler SJ. Childhood asthma: new insights into management. J Allergy Clin Immunol. 2002;109:3–13. [PubMed:11799358]CrossRefGoogle Scholar
  26. 26.
    Keskin O, Uluca U, Birben E, Coskun Y, MY Ozkars MK, Kucukosmanoglu E, Kalayci O. Genetic associations of the response to inhaled corticosteroids in children during an asthma exacerbation. Pediatr Allergy Immunol. 2016;27:507–13. [PubMed:27003716]CrossRefGoogle Scholar
  27. 27.
    Weiss ST, Lake SL, Silverman ES, EK Silverman BR, Drazen JM, Tantisira KG. Asthma steroid pharmacogenetics: a study strategy to identify replicated treatment responses. Proc Am Thorac Soc. 2004;1:364–7. [PubMed:16113459]CrossRefGoogle Scholar
  28. 28.
    Mukherjee M, Svenningsen S, Nair P. Glucocortiosteroid subsensitivity and asthma severity. Curr Opin Pulm Med. 2017;23:78–88. [PubMed:27801710]CrossRefGoogle Scholar
  29. 29.
    Ortega VE, Meyers DA, Bleecker ER. Asthma pharmacogenetics and the development of genetic profiles for personalized medicine. Pharmgenomics Pers Med. 2015;8:9–22. [PubMed:25691813]PubMedPubMedCentralGoogle Scholar
  30. 30.
    Panek M, Pietras T, Antczak A, Fabijan A, Przemecka M, Gorski P, Kuna P, Szemraj J. The N363S and I559N single nucleotide polymorphisms of the h-GR/NR3C1 gene in patients with bronchial asthma. Int J Mol Med. 2012;30:142–50. [PubMed:22469783]PubMedGoogle Scholar
  31. 31.
    Pietras T, Panek M, Tworek D, Oszajca K, Wujcik R, Gorski P, Kuna P, Szemraj J. The Bcl I single nucleotide polymorphism of the human glucocorticoid receptor gene h-GR/NR3C1 promoter in patients with bronchial asthma: pilot study. Mol Biol Rep. 2011;38:3953–8. [PubMed:21113676]CrossRefGoogle Scholar
  32. 32.
    Hawkins GA, Amelung PJ, Smith RS, Jongepier H, Howard TD, Koppelman GH, Meyers DA, Bleecker ER, Postma DS. Identification of polymorphisms in the human glucocorticoid receptor gene (NR3C1) in a multi-racial asthma case and control screening panel. DNA Seq. 2004;15:167–73. sCrossRefGoogle Scholar
  33. 33.
    Panek M, Pietras T, Antczak A, Gorski P, Kuna P, Szemraj J. The role of functional single nucleotide polymorphisms of the human glucocorticoid receptor gene NR3C1 in Polish patients with bronchial asthma. Mol Biol Rep. 2012;39:4749–57. [PubMed:22015776]CrossRefGoogle Scholar
  34. 34.
    Panek M, Pietras T, Fabijan A, Ziolo J, Wieteska L, Malachowska B, Fendler W, Szemraj J, Kuna P. The NR3C1 glucocorticoid receptor gene polymorphisms may modulate the TGF-beta mRNA expression in asthma patients. Inflammation. 2015;38:1479–92. [PubMed:25649164]CrossRefGoogle Scholar
  35. 35.
    Panek M, Pietras T, Szemraj J, Kuna P. Association analysis of the glucocorticoid receptor gene (NR3C1) haplotypes (ER22/23EK, N363S, BclI) with mood and anxiety disorders in patients with asthma. Exp Ther Med. 2014;8:662–70. [PubMed:25009637]CrossRefGoogle Scholar
  36. 36.
    Cheng Z, Dai LL, Liu Q, Liu M, Wang Q, Li PF, Wang H, Jia LQ, An L. Correlation between polymorphisms in the glucocorticoid receptor gene NR3C1 and susceptibility to asthma in a Chinese population from the Henan Province. Genet Mol Res. 2016;15. gmr.15028507. [PubMed:27323143]Google Scholar
  37. 37.
    Huang YJ, Nariya S, Harris JM, Lynch SV, Choy DF, Arron JR, Boushey H. The airway microbiome in patients with severe asthma: Associations with disease features and severity. J Allergy Clin Immunol. 2015;136:874–84. [PubMed:26220531]CrossRefGoogle Scholar
  38. 38.
    Karagiannidis C, et al. Glucocorticoids upregulate FOXP3 expression and regulatory T cells in asthma. J Allergy Clin Immunol. 2004;114:1425–33. [PubMed:15577848]CrossRefGoogle Scholar
  39. 39.
    Izuhara Y, et al. GLCCI1 variant accelerates pulmonary function decline in patients with asthma receiving inhaled corticosteroids. Allergy. 2014;69:668–73. [PubMed:24673601]CrossRefGoogle Scholar
  40. 40.
    Raby BA, Van Steen K, Lasky-Su J, Tantisira K, Kaplan F, Weiss ST. Importin-13 genetic variation is associated with improved airway responsiveness in childhood asthma. Respir Res. 2009;10:67.[PubMed:19619331]CrossRefGoogle Scholar
  41. 41.
    Sayers I, Hall IP. Pharmacogenetic approaches in the treatment of asthma. Curr Allergy Asthma Rep. 2005;5:101–8. [PubMed:15683609]CrossRefGoogle Scholar
  42. 42.
    Dijkstra A, Koppelman GH, Vonk JM, Bruinenberg M, Schouten JP, Postma DS. Pharmacogenomics and outcome of asthma: no clinical application for long-term steroid effects by CRHR1 polymorphisms. J Allergy Clin Immunol. 2008;121:1510–3. [PubMed:18539200]CrossRefGoogle Scholar
  43. 43.
    Poon AH, et al. Association of corticotropin-releasing hormone receptor-2 genetic variants with acute bronchodilator response in asthma. Pharmacogenet Genomics. 2008;18:373–82. [PubMed:18408560]CrossRefGoogle Scholar
  44. 44.
    Puthothu B, Bierbaum S, MV Kopp JF, Heinze J, Weckmann M, Krueger M, Heinzmann A. Association of TNF-alpha with severe respiratory syncytial virus infection and bronchial asthma. Pediatr Allergy Immunol. 2009;20:157–63. [PubMed:18811622]CrossRefGoogle Scholar
  45. 45.
    Cuzzoni E, et al. Glucocorticoid pharmacogenetics in pediatric idiopathic nephrotic syndrome. Pharmacogenomics. 2015;16:1631–48. [PubMed:26419298]CrossRefGoogle Scholar
  46. 46.
    Yang G, Chen J, Xu F, Bao Z, Yao Y, Zhou J. Association between tumor necrosis factor-alpha rs1800629 polymorphism and risk of asthma: a meta-analysis. PLoS One. 2014;9:e99962. [PubMed:24936650]CrossRefGoogle Scholar
  47. 47.
    MacIntyre EA, et al. Traffic, asthma and genetics: combining international birth cohort data to examine genetics as a mediator of traffic-related air pollution’s impact on childhood asthma. Eur J Epidemiol. 2013;28:597–606. [PubMed:23880893]CrossRefGoogle Scholar
  48. 48.
    Choi WA, et al. Gene-gene interactions between candidate gene polymorphisms are associated with total IgE levels in Korean children with asthma. J Asthma. 2012;49:243–52. [PubMed:22376040]CrossRefGoogle Scholar
  49. 49.
    Yucesoy B, et al. Genetic variants in TNFalpha, TGFB1, PTGS1 and PTGS2 genes are associated with diisocyanate-induced asthma. J Immunotoxicol. 2016;13:119–26. [PubMed:25721048]CrossRefGoogle Scholar
  50. 50.
    He Y, Peng S, Xiong W, Xu Y, Liu J. Association between polymorphism of interleukin-1 beta and interleukin-1 receptor antagonist gene and asthma risk: a meta-analysis. Sci World J. 2015;2015:685684. [PubMed:25821855]Google Scholar
  51. 51.
    Kosugi EM, de Camargo-Kosugi CM, Hirai ER, Mendes-Neto JA, Gregorio LC, Guerreiro-da-Silva ID, Weckx LL. Interleukin-6 -174 G/C promoter gene polymorphism in nasal polyposis and asthma. Rhinology. 2013;51:70–6. [PubMed:23441314]PubMedGoogle Scholar
  52. 52.
    Li F, Xie X, Li S, Ke R, Zhu B, Yang L, Li M. Interleukin-6 gene -174G/C polymorphism and bronchial asthma risk: a meta-analysis. Int J Clin Exp Med. 2015;8:12601–8. [PubMed:26550171]PubMedPubMedCentralGoogle Scholar
  53. 53.
    Zhang JH, Zhou GH, Wei TT, Chang ZS. Association between the interleukin 4 gene -590C > T promoter polymorphism and asthma in Xinjiang Uighur children. Genet Mol Res. 2016;15. gmr.15038363. [PubMed:27525870]Google Scholar
  54. 54.
    Zhu N, Gong Y, XD Chen JZ, Long F, He J, JW Xia LD. Association between the polymorphisms of interleukin-4, the interleukin-4 receptor gene and asthma. Chin Med J (Engl). 2013;126:2943–51. [PubMed:23924473]Google Scholar
  55. 55.
    Hwang Y, Suk S, YR Shih TS, Du B, Xie Y, Li Z, Varghese S. WNT3A promotes myogenesis of human embryonic stem cells and enhances in vivo engraftment. Sci Rep. 2014;4:5916. [PubMed:25084050]CrossRefGoogle Scholar
  56. 56.
    Battle NC, 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;175:881–7. [PubMed:17303794]CrossRefGoogle Scholar
  57. 57.
    Beghe B, Hall IP, Parker SG, MF Moffatt AW, Connolly MJ, Fabbri LM, Ruse C, Sayers I. Polymorphisms in IL13 pathway genes in asthma and chronic obstructive pulmonary disease. Allergy. 2010;65:474–81. [PubMed:19796199]CrossRefGoogle Scholar
  58. 58.
    Xi D, Pan S, Cui T, Wu J. Association between IL-13 gene polymorphism and asthma in Han nationality in Hubei Chinese population. J Huazhong Univ Sci Technolog Med Sci. 2004;24:219–22. [PubMed:15315330]CrossRefGoogle Scholar
  59. 59.
    Tantisira KG, et al. Genomewide association between GLCCI1 and response to glucocorticoid therapy in asthma. N Engl J Med. 2011;365:1173–83. [PubMed:21991891]CrossRefGoogle Scholar
  60. 60.
    Hosking L, Bleecker E, Ghosh S, Yeo A, Jacques L, Mosteller M, Meyers D. GLCCI1 rs37973 does not influence treatment response to inhaled corticosteroids in white subjects with asthma. J Allergy Clin Immunol. 2014;133:587–9. [PubMed:24131825]CrossRefGoogle Scholar
  61. 61.
    Hu C, Xun Q, Li X, He R, Lu R, Zhang S, Hu X, Feng J. GLCCI1 variation is associated with asthma susceptibility and inhaled corticosteroid response in a Chinese Han population. Arch Med Res. 2016;47:118–25. [PubMed:27133712]CrossRefGoogle Scholar
  62. 62.
    El-Adly TZ, Kamal S, Selim H, Botros S. Association of macrophage migration inhibitory factor promoter polymorphism -173G/C with susceptibility to childhood asthma. Cent Eur J Immunol. 2016;41:268–72. [PubMed:27833444]CrossRefGoogle Scholar
  63. 63.
    Tantisira KG, et al. Genome-wide association identifies the T gene as a novel asthma pharmacogenetic locus. Am J Respir Crit Care Med. 2012;185:1286–91. [PubMed:22538805]CrossRefGoogle Scholar
  64. 64.
    Stockmann C, et al. Fluticasone propionate pharmacogenetics: CYP3A4*22 polymorphism and pediatric asthma control. J Pediatr. 2013;162:1222–7. 1227 e1–2.[PubMed:23290512]CrossRefGoogle Scholar
  65. 65.
    Ye YM, Lee HY, Kim SH, Jee YK, Lee SK, Lee SH, Park HS. Pharmacogenetic study of the effects of NK2R G231E G > A and TBX21 H33Q C > G polymorphisms on asthma control with inhaled corticosteroid treatment. J Clin Pharm Ther. 2009;34:693–701. [PubMed:20175803]CrossRefGoogle Scholar
  66. 66.
    Berce V, Kozmus CE, Potocnik U. Association among ORMDL3 gene expression, 17q21 polymorphism and response to treatment with inhaled corticosteroids in children with asthma. Pharmacogenomics J. 2013;13:523–9. [PubMed:22986918]CrossRefGoogle Scholar
  67. 67.
    Lima JJ. Treatment heterogeneity in asthma: genetics of response to leukotriene modifiers. Mol Diagn Ther. 2007;11:97–104. [PubMed:17397245]CrossRefGoogle Scholar
  68. 68.
    Sanz C, Isidro-Garcia M, Davila I, Moreno E, Laffond E, Lorente F. Analysis of 927 T > C CYSLTRI and -444A > C LTC4S polymorphisms in patients with asthma. J Investig Allergol Clin Immunol. 2006;16:331–7. [PubMed:17153879]PubMedGoogle Scholar
  69. 69.
    Thompson MD, Capra V, Clunes MT, Rovati GE, Stankova J, Maj MC, Duffy DL. Cysteinyl leukotrienes pathway genes, atopic asthma and drug response: from population isolates to large genome-wide association studies. Front Pharmacol. 2016;7:299. [PubMed:27990118]CrossRefGoogle Scholar
  70. 70.
    Pillai SG, et al. Factor analysis in the Genetics of Asthma International Network family study identifies five major quantitative asthma phenotypes. Clin Exp Allergy. 2008;38:421–9. [PubMed:18177490]CrossRefGoogle Scholar
  71. 71.
    Hong X, Zhou H, Tsai HJ, Wang X, Liu X, Wang B, Xu X, Xu X. Cysteinyl leukotriene receptor 1 gene variation and risk of asthma. Eur Respir J. 2009;33:42–8. [PubMed:18829683]CrossRefGoogle Scholar
  72. 72.
    Kumar A, Sharma S, Agrawal A, Ghosh B. Association of the -1072G/A polymorphism in the LTC4S gene with asthma in an Indian population. Int Arch Allergy Immunol. 2012;159:271–7. [PubMed:22722751]CrossRefGoogle Scholar
  73. 73.
    Lee SY, Kim HB, Kim JH, Kim BS, Kang MJ, Jang SO, Seo HJ, Hong SJ. Responsiveness to montelukast is associated with bronchial hyperresponsiveness and total immunoglobulin E but not polymorphisms in the leukotriene C4 synthase and cysteinyl leukotriene receptor 1 genes in Korean children with exercise-induced asthma (EIA). Clin Exp Allergy. 2007;37:1487–93. [PubMed:17883728]PubMedGoogle Scholar
  74. 74.
    Telleria JJ, Blanco-Quiros A, Varillas D, Armentia A, Fernandez-Carvajal I, Jesus Alonso M, Diez I. ALOX5 promoter genotype and response to montelukast in moderate persistent asthma. Respir Med. 2008;102:857–61. [PubMed:18339529]CrossRefGoogle Scholar
  75. 75.
    Mougey E, JE Lang HA, Teague WG, Dozor AJ, Wise RA, Lima JJ. ALOX5 polymorphism associates with increased leukotriene production and reduced lung function and asthma control in children with poorly controlled asthma. Clin Exp Allergy. 2013;43:512–20. [PubMed:23600541]CrossRefGoogle Scholar
  76. 76.
    Kotani H, et al. Influence of leukotriene pathway polymorphisms on clinical responses to montelukast in Japanese patients with asthma. J Clin Pharm Ther. 2012;37:112–6. [PubMed:21385196]CrossRefGoogle Scholar
  77. 77.
    Sayers I, et al. Promoter polymorphism in the 5-lipoxygenase (ALOX5) and 5-lipoxygenase-activating protein (ALOX5AP) genes and asthma susceptibility in a Caucasian population. Clin Exp Allergy. 2003;33:1103–10. [PubMed:12911785]CrossRefGoogle Scholar
  78. 78.
    Berghea EC, Popa LO, Dutescu MI, Meirosu M, IC Farcasanu FB, Bara C, Popa OM. Association of leukotriene C4 synthase A-444C polymorphism with asthma and asthma phenotypes in Romanian population. Maedica (Buchar). 2015;10:91–6. [PubMed:28275397]Google Scholar
  79. 79.
    Zhang Y, Huang H, Huang J, Xiang Z, Yang M, Tian C, Fan H. The -444A/C polymorphism in the LTC4S gene and the risk of asthma: a meta-analysis. Arch Med Res. 2012;43:444–50. [PubMed:22884858]CrossRefGoogle Scholar
  80. 80.
    Lima JJ. Genetic influences on response to asthma pharmacotherapy. Expert Rev Clin Pharmacol. 2008;1:649–60. [PubMed:24422736]CrossRefGoogle Scholar
  81. 81.
    Tantisira KG, Lima J, Sylvia J, Klanderman B, Weiss ST. 5-lipoxygenase pharmacogenetics in asthma: overlap with Cys-leukotriene receptor antagonist loci. Pharmacogenet Genomics. 2009;19:244–7. [PubMed:19214143]CrossRefGoogle Scholar
  82. 82.
    Alizadeh Z, Mortaz E, Adcock I, Moin M. Role of epigenetics in the pathogenesis of asthma. Iran J Allergy Asthma Immunol. 2017;16:82–91. [PubMed:28601047]PubMedGoogle Scholar
  83. 83.
    Loffredo LF, Abdala-Valencia H, KR Anekalla LC-P, CJ Gottardi SB. Beyond epithelial-to-mesenchymal transition: Common suppression of differentiation programs underlies epithelial barrier dysfunction in mild, moderate, and severe asthma. Allergy. 2017;72(12):1988–2004. [PubMed:28599074]CrossRefGoogle Scholar
  84. 84.
    Ji H. JM Biagini Myers, EB Brandt, C Brokamp, PH Ryan, GK Khurana Hershey, Air pollution, epigenetics, and asthma. Allergy Asthma Clin Immunol. 2016;12:51. [PubMed:27777592]CrossRefGoogle Scholar
  85. 85.
    Chogtu B, Bhattacharjee D, Magazine R. Epigenetics: the new frontier in the landscape of asthma. Scientifica (Cairo). 2016;2016:4638949. [PubMed:27293973]Google Scholar
  86. 86.
    Wysocki K, Conley Y, Wenzel S. Epigenome variation in severe asthma. Biol Res Nurs. 2015;17:263–9. [PubMed:25288825]CrossRefGoogle Scholar
  87. 87.
    Ducharme FM, et al. Determinants Of Oral corticosteroid Responsiveness in Wheezing Asthmatic Youth (DOORWAY): protocol for a prospective multicentre cohort study of children with acute moderate-to-severe asthma exacerbations. BMJ Open. 2014;4:e004699. [PubMed:24710133]CrossRefGoogle Scholar
  88. 88.
    Norman G, et al. Omalizumab for the treatment of severe persistent allergic asthma: a systematic review and economic evaluation. Health Technol Assess. 2013;17:1–342. [PubMed:24267198]CrossRefGoogle Scholar
  89. 89.
    Farzan N, et al. Rationale and design of the multiethnic pharmacogenomics in childhood asthma consortium. Pharmacogenomics. 2017;18:931–43. [PubMed:28639505]CrossRefGoogle Scholar
  90. 90.
    Loisel DA, et al. Genetic associations with viral respiratory illnesses and asthma control in children. Clin Exp Allergy. 2016;46:112–24. [PubMed:26399222]CrossRefGoogle Scholar
  91. 91.
    Turner S, et al. Childhood asthma exacerbations and the Arg16 beta2-receptor polymorphism: a meta-analysis stratified by treatment. J Allergy Clin Immunol. 2016;138:107–13. e5.[PubMed:26774659]CrossRefGoogle Scholar
  92. 92.
    Miller SM, Ortega VE. Pharmacogenetics and the development of personalized approaches for combination therapy in asthma. Curr Allergy Asthma Rep. 2013;13:443–52. [PubMed:23912588]CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Department of PharmacyShanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghaiChina

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