Skip to main content

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 448))

Summary

Asthma is a common disease characterized by airway inflammation and bronchorestriction. There are several common categories of medications for treating asthma; however, not all asthmatics have the same response to these medications, some of which are adverse responses that are potentially life threatening. Because interindividual responses to asthma medications can vary considerably, the potential for genetic contributions to variable drug responses is significant. This chapter reviews the most common biological pathways targeted by asthma therapy and briefly discusses the genetic contribution to varied responses to asthma therapy for four common types of asthma medications: β-agonists, anticholinergics, leukotriene modifiers, and corticosteroids.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Busse WW, Lemanske RF Jr. (2001) Asthma. N Engl J Med. 344, 350–362.

    CAS  PubMed  Google Scholar 

  2. Koppelman GH, Meijer GG, Postma DS. (1999) Defining asthma in genetic studies. Clin Exp Allergy. 29(suppl. 4), 1–4.

    PubMed  Google Scholar 

  3. Panhuysen CI, Meyers DA, Postma DS, Bleecker ER. (1995) The genetics of asthma and atopy. Allergy, 50, 863–869.

    CAS  PubMed  Google Scholar 

  4. Tattersfield AE, Knox AJ, Britton JR, Hall IP. (2002) Asthma. Lancet. 360, 1313–1322.

    CAS  PubMed  Google Scholar 

  5. Braman SS. (2006) The global burden of asthma. Chest. 130(1 suppl.), 4S–12S.

    PubMed  Google Scholar 

  6. Masoli M, Fabian D, Holt S, Beasley R. (2004) The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy. 59, 469–478.

    PubMed  Google Scholar 

  7. National Asthma Education and Prevention Program. (1997) Expert panel report 2. Guidelines for the diagnosis and management of asthma. Bethesda, MD: National Institutes of Health. NIH publication 97–4051.

    Google Scholar 

  8. National Asthma Education and Prevention Program. (2002) Executive summary of the NAREPP expert panel report. Guidelines for the diagnosis and management of asthma. Update on selected topics 2002. Bethesda, MD: National Institutes of Health. NIH publication 02–5075.

    Google Scholar 

  9. Drazen JM, Silverman EK, Lee TH. (2000) Heterogeneity of therapeutic responses in asthma. Br Med Bull. 56, 1054–1070.

    CAS  PubMed  Google Scholar 

  10. Weiss ST, Litonjua AA, Lange C et al. (2006) Overview of the pharmacogenetics of asthma treatment. Pharmacogenomics J. 6, 311–326.

    CAS  PubMed  Google Scholar 

  11. Israel E, Drazen JM, Liggett SB, et al. (2001) Effect of polymorphism of the beta(2)-adrenergic receptor on response to regular use of albuterol in asthma. Int Arch Allergy Immunol. 124, 183–186.

    CAS  PubMed  Google Scholar 

  12. Eichelbaum M, Ingelman-Sundberg M, Evans WE. (2006) Pharmacogenomics and individualized drug therapy. Annu Rev Med. 57, 119–137.

    CAS  PubMed  Google Scholar 

  13. Drazen JM, Yandava CN, Dube L, et al. (1999) Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment. Nat Genet. 22, 168–170.

    CAS  PubMed  Google Scholar 

  14. Loke TK, Sousa AR, Corrigan CJ, Lee TH. (2002) Glucocorticoid-resistant asthma. Curr Allergy Asthma Rep. 2, 144–150.

    PubMed  Google Scholar 

  15. Sampson AP, Siddiqui S, Buchanan D, et al. (2000) Variant LTC(4) synthase allele modifies cysteinyl leukotriene synthesis in eosinophils and predicts clinical response to zafirlukast. Thorax. 55(suppl. 2), S28S31.

    PubMed  Google Scholar 

  16. Sousa AR, Lane SJ, Cidlowski JA, Staynov DZ, Lee TH. (2000) Glucocorticoid resistance in asthma is associated with elevated in vivo expression of the glucocorticoid receptor betaisoform. J Allergy Clin Immunol. 105, 943–950.

    CAS  PubMed  Google Scholar 

  17. Malmstrom K, Rodriguez-Gomez G, Guerra J, et al. (1999) Oral montelukast, inhaled beclomethasone, and placebo for chronic asthma. A randomized, controlled trial. Montelukast/ Beclomethasone Study Group. Ann Intern Med. 130, 487–495.

    CAS  PubMed  Google Scholar 

  18. Liggett SB. (2001) Pharmacogenetic applications of the Human Genome project. Nat Med. 7, 281–283.

    CAS  PubMed  Google Scholar 

  19. Nelson HS, Weiss ST, Bleecker ER, Yancey SW, Dorinsky PM. (2006) The Salmeterol Multicenter Asthma Research Trial: a comparison of usual pharmacotherapy for asthma or usual pharmacotherapy plus salmeterol. Chest. 129, 15–26.

    CAS  PubMed  Google Scholar 

  20. Sears MR, Taylor DR. (1993) Bronchodilator treatment in asthma. Increase in deaths during salmeterol treatment unexplained. BMJ. 306, 1610–1611.

    CAS  PubMed  Google Scholar 

  21. Taylor DR, Sears MR, Herbison GP, et al. (1993) Regular inhaled beta agonist in asthma: effects on exacerbations and lung function. Thorax. 48, 134–138.

    CAS  PubMed  Google Scholar 

  22. Taylor DR, Sears MR. (1994) Regular beta-adrenergic agonists. Evidence, not reassurance, is what is needed. Chest. 106, 552–559.

    CAS  PubMed  Google Scholar 

  23. Lanes SF, Garcia Rodriguez LA, Huerta C. (2002) Respiratory medications and risk of asthma death. Thorax. 57, 683–686.

    CAS  PubMed  Google Scholar 

  24. Lanes SF, Lanza LL, Wentworth CE, III. (1998) Risk of emergency care, hospitalization, and ICU stays for acute asthma among recipients of salmeterol. Am J Respir Crit Care Med. 158, 857–861.

    CAS  PubMed  Google Scholar 

  25. Rea HH, Garrett JE, Lanes SF, Birmann BM, Kolbe J. (1996) The association between asthma drugs and severe life-threatening attacks. Chest. 110, 1446–1451.

    CAS  PubMed  Google Scholar 

  26. Garrett JE, Lanes SF, Kolbe J, Rea HH. (1996) Risk of severe life threatening asthma and beta agonist type: an example of confounding by severity. Thorax. 51, 1093–1099.

    CAS  PubMed  Google Scholar 

  27. Poole C, Lanes SF, Walker AM. (1990) Fenoterol and fatal asthma. Lancet. 335, 920.

    CAS  PubMed  Google Scholar 

  28. Tantisira KG, Drazen JM. (2005) Pharmacogenetics. In: Silverman EK, Shapiro SD, Lomas DA, Weiss ST, eds. Respiratory genetics. London: Hodder Education; 191–216.

    Google Scholar 

  29. Dawson B., Trapp RG. (2004) Research questions about means in three of more groups. Basic and clinical biostatistics. 4th ed. New York: Lange Medical Books/McGraw-Hill; 162–189.

    Google Scholar 

  30. Magi R, Kaplinski L, Remm M. (2006) The whole genome tagSNP selection and transferability among HapMap populations. Pac Symp Biocomput. 535–543.

    Google Scholar 

  31. Brooks LD. (2006) Using the HapMap in drug development. Clin Adv Hematol Oncol. 4, 423–424.

    PubMed  Google Scholar 

  32. Barnes MR. (2006) Navigating the HapMap. Brief Bioinform. 7, 211–224.

    CAS  PubMed  Google Scholar 

  33. O'Shaughnessy KM. (2006) HapMap, pharmacogenomics, and the goal of personalized prescribing. Br J Clin Pharmacol. 61, 783–786.

    PubMed  Google Scholar 

  34. Andrawiss M. (2005) First phase of HapMap project already helping drug discovery. Nat Rev Drug Discov. 4, 947.

    CAS  PubMed  Google Scholar 

  35. Lin M, Aquilante C, Johnson JA, Wu R. (2005) Sequencing drug response with HapMap. Pharmacogenomics J. 5, 149–156.

    CAS  PubMed  Google Scholar 

  36. Barrett JC, Fry B, Maller J, Daly MJ. (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 21, 263–265.

    CAS  PubMed  Google Scholar 

  37. Kraft P. (2006) Efficient two-stage genome-wide association designs based on false positive report probabilities. Pac Symp Biocomput. 523–534.

    Google Scholar 

  38. Wiltshire S, de Bakker PI, Daly MJ. (2006) The value of gene-based selection of tag SNPs in genome-wide association studies. Eur J Hum Genet. 14, 1209–1214.

    CAS  PubMed  Google Scholar 

  39. Wang H, Thomas DC, Pe'er I, Stram DO. (2006) Optimal two-stage genotyping designs for genome-wide association scans. Genet Epidemiol. 30, 356–368.

    PubMed  Google Scholar 

  40. Hirschhorn JN, Daly MJ. (2005) Genome-wide association studies for common diseases and complex traits. Nat Rev Genet. 6, 95–108.

    CAS  PubMed  Google Scholar 

  41. Saito A, Kamatani N. (2002) Strategies for genome-wide association studies: optimization of study designs by the stepwise focusing method. J Hum Genet. 47, 360–365.

    CAS  PubMed  Google Scholar 

  42. Ohnishi Y, Tanaka T, Ozaki K, Yamada R, Suzuki H, Nakamura Y. (2001) A high-throughput SNP typing system for genome-wide association studies. J Hum Genet. 46, 471–477.

    CAS  PubMed  Google Scholar 

  43. Barrett JC, Cardon LR. (2006) Evaluating coverage of genome-wide association studies. Nat Genet. 38, 659–662.

    CAS  PubMed  Google Scholar 

  44. Evans DM, Cardon LR. (2006) Genome-wide association: a promising start to a long race. Trends Genet. 22, 350–354.

    CAS  PubMed  Google Scholar 

  45. Yang Q, Cui J, Chazaro I, Cupples LA, Demissie S. (2005) Power and type I error rate of false discovery rate approaches in genome-wide association studies. BMC Genet. 6(suppl 1), S134.

    PubMed  Google Scholar 

  46. Wang WY, Barratt BJ, Clayton DG, Todd JA. (2005) Genome-wide association studies: theoretical and practical concerns. Nat Rev Genet. 6, 109–118.

    CAS  PubMed  Google Scholar 

  47. Hawkins GA, Tantisira K, Meyers DA, et al. (2006) Sequence, haplotype and association analysis of ADR{beta}2 in multi-ethnic asthma case/control subjects. Am J Respir Crit Care Med. 174, 1101–1109.

    CAS  PubMed  Google Scholar 

  48. Reihsaus E, Innis M, MacIntyre N, Liggett SB. (1993) Mutations in the gene encoding for the beta 2-adrenergic receptor in normal and asthmatic subjects. Am J Respir Cell Mol Biol. 8, 334–339.

    CAS  PubMed  Google Scholar 

  49. Green SA, Turki J, Innis M, Liggett SB. (1994) Amino-terminal polymorphisms of the human beta 2-adrenergic receptor impart distinct agonist-promoted regulatory properties. Biochemistry. 33, 9414–9419.

    CAS  PubMed  Google Scholar 

  50. Martinez FD, Graves PE, Baldini M, Solomon S, Erickson R. (1997) Association between genetic polymorphisms of the beta2-adrenoceptor and response to albuterol in children with and without a history of wheezing. J Clin Invest. 100, 3184–3188.

    CAS  PubMed  Google Scholar 

  51. Cho SH, Oh SY, Bahn JW, et al. (2005) Association between bronchodilating response to short-acting beta-agonist and non-synonymous single-nucleotide polymorphisms of betaadrenoceptor gene. Clin Exp Allergy. 35, 1162–1167.

    CAS  PubMed  Google Scholar 

  52. Kotani Y, Nishimura Y, Maeda H, Yokoyama M. (1999) Beta2-Adrenergic receptor polymorphisms affect airway responsiveness to salbutamol in asthmatics. J Asthma. 36, 583–590.

    CAS  PubMed  Google Scholar 

  53. Lima JJ, Thomason DB, Mohamed MH, Eberle LV, Self TH, Johnson JA. (1999) Impact of genetic polymorphisms of the beta2-adrenergic receptor on albuterol bronchodilator pharmacodynamics. Clin Pharmacol Ther. 65, 519–525.

    CAS  PubMed  Google Scholar 

  54. Tan S, Hall IP, Dewar J, Dow E, Lipworth B. (1997) Association between beta 2-adrenocep-tor polymorphism and susceptibility to bronchodilator desensitisation in moderately severe stable asthmatics. Lancet. 350, 995–999.

    CAS  PubMed  Google Scholar 

  55. Hancox RJ, Sears MR, Taylor DR. (1998) Polymorphism of the beta2-adrenoceptor and the response to long-term beta2-agonist therapy in asthma. Eur Respir J. 11, 589–593.

    CAS  PubMed  Google Scholar 

  56. Israel E, Chinchilli VM, Ford JG, et al. (2004) Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial. Lancet. 364, 1505–1512.

    CAS  PubMed  Google Scholar 

  57. Taylor DR, Drazen JM, Herbison GP, Yandava CN, Hancox RJ, Town GI. (2000) Asthma exacerbations during long term beta agonist use: influence of beta(2) adrenoceptor polymorphism. Thorax. 55, 762–767.

    CAS  PubMed  Google Scholar 

  58. Israel E, Drazen JM, Liggett SB, et al. (2000) The effect of polymorphisms of the beta(2)-adrenergic receptor on the response to regular use of albuterol in asthma. Am J Respir Crit Care Med. 162, 75–80.

    CAS  PubMed  Google Scholar 

  59. Burchard EG, Avila PC, Nazario S, et al. (2004) Lower bronchodilator responsiveness in Puerto Rican than in Mexican subjects with asthma. Am J Respir Crit Care Med. 169, 386–392.

    PubMed  Google Scholar 

  60. Choudhry S, Ung N, Avila PC, et al. (2005) Pharmacogenetic differences in response to albuterol between Puerto Ricans and Mexicans with asthma. Am J Respir Crit Care Med. 171, 563–570.

    PubMed  Google Scholar 

  61. Drysdale CM, McGraw DW, Stack CB, et al. (2000) Complex promoter and coding region beta 2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness. Proc Natl Acad Sci U S A. 97, 10483–10488.

    CAS  PubMed  Google Scholar 

  62. Johnatty SE, Abdellatif M, Shimmin L, Clark RB, Boerwinkle E. (2002) Beta 2 adrenergic receptor 5' haplotypes influence promoter activity. Br J Pharmacol. 137, 1213–1216.

    CAS  PubMed  Google Scholar 

  63. McGraw DW, Forbes SL, Kramer LA, Liggett SB. (1998) Polymorphisms of the 5′ leader cistron of the human beta2-adrenergic receptor regulate receptor expression. J Clin Invest. 102, 1927–1932.

    CAS  PubMed  Google Scholar 

  64. McGraw DW, Liggett SB. (1999) Coding block and 5 leader cistron polymorphisms of the beta2-adrenergic receptor. Clin Exp Allergy. 29(suppl. 4), 43–45.

    CAS  PubMed  Google Scholar 

  65. Parola AL, Kobilka BK. (1994) The peptide product of a 5′ leader cistron in the beta 2 adrenergic receptor mRNA inhibits receptor synthesis. J Biol Chem. 269, 4497–4505.

    CAS  PubMed  Google Scholar 

  66. Scott MG, Swan C, Wheatley AP, Hall IP. (1999) Identification of novel polymorphisms within the promoter region of the human beta2 adrenergic receptor gene. Br J Pharmacol. 126, 841–844.

    CAS  PubMed  Google Scholar 

  67. Timmermann B, Li GH, Luft FC, Lund-Johansen P, Skrabal F, Hoehe MR. (1998) Novel DNA sequence differences in the beta2-adrenergic receptor gene promoter region. Hum Mutat. 11, 343–344.

    CAS  PubMed  Google Scholar 

  68. Taylor DR, Epton MJ, Kennedy MA, et al. (2005) Bronchodilator response in relation to beta2-adrenoceptor haplotype in patients with asthma. Am J Respir Crit Care Med. 172, 700–703.

    PubMed  Google Scholar 

  69. Dishy V, Landau R, Sofowora GG, et al. (2004) Beta2-adrenoceptor Thr164Ile polymorphism is associated with markedly decreased vasodilator and increased vasoconstrictor sensitivity in vivo. Pharmacogenetics. 14, 517–522.

    CAS  PubMed  Google Scholar 

  70. Fenech A, Hall IP. (2002) Pharmacogenetics of asthma. Br J Clin Pharmacol. 53, 3–15.

    CAS  PubMed  Google Scholar 

  71. Fenech AG, Ebejer MJ, Felice AE, Ellul-Micallef R, Hall IP. (2001) Mutation screening of the muscarinic M(2) and M(3) receptor genes in normal and asthmatic subjects. Br J Pharmacol. 133, 43–48.

    CAS  PubMed  Google Scholar 

  72. Wang JC, Hinrichs AL, Stock H, et al. (2004) Evidence of common and specific genetic effects: association of the muscarinic acetylcholine receptor M2 (CHRM2) gene with alcohol dependence and major depressive syndrome. Hum Mol Genet. 13, 1903–1911.

    CAS  PubMed  Google Scholar 

  73. Donfack J, Kogut P, Forsythe S, Solway J, Ober C. (2003) Sequence variation in the promoter region of the cholinergic receptor muscarinic 3 gene and asthma and atopy. J Allergy Clin Immunol. 111, 527–532.

    CAS  PubMed  Google Scholar 

  74. Yamamoto T, Yamashita N, Kuwabara M, et al. (2002) Mutation screening of the muscarinic m2 and m3 receptor genes in asthmatics, outgrow subjects, and normal controls. Ann Genet. 45, 109–113.

    PubMed  Google Scholar 

  75. tera-Wadleigh SD, Wiesch D, Bonner TI. (1989) An SstI polymorphism for the human muscarinic acetylcholine receptor gene, m4 (CHRM 4). Nucleic Acids Res. 17, 6431.

    Google Scholar 

  76. McGraw DW, Almoosa KF, Paul RJ, Kobilka BK, Liggett SB. (2003) Antithetic regulation by beta-adrenergic receptors of Gq receptor signaling via phospholipase C underlies the airway beta-agonist paradox. J Clin Invest. 112, 619–626.

    CAS  PubMed  Google Scholar 

  77. Szalai C, Tolgyesi G, Nagy A, Falus A. (2006) Pharmacogenomics of asthma: present and perspective. Orv Hetil. 147, 159–169.

    PubMed  Google Scholar 

  78. Israel E. (2005) Genetics and the variability of treatment response in asthma. J Allergy Clin Immunol. 115(4 suppl.), S532–S538.

    CAS  PubMed  Google Scholar 

  79. Samuelsson B, Funk CD. (1989) Enzymes involved in the biosynthesis of leukotriene B4. J Biol Chem. 264, 19469–19472.

    CAS  PubMed  Google Scholar 

  80. Samuelsson B, Haeggstrom JZ, Wetterholm A. (1991) Leukotriene biosynthesis. Ann N Y Acad Sci. 629, 89–99.

    CAS  PubMed  Google Scholar 

  81. Drazen JM. (1995) Leukotrienes. In: Busse W.W., Holgate ST, eds. Asthma and rhinitis. Boston: Blackwell Scientific; 838–850.

    Google Scholar 

  82. Hall IP. (2000) Pharmacogenetics of asthma. Eur Respir J. 15, 449–451.

    CAS  PubMed  Google Scholar 

  83. Hui Y, Funk CD. (2002) Cysteinyl leukotriene receptors. Biochem Pharmacol. 64, 1549–1557.

    CAS  PubMed  Google Scholar 

  84. Coffey M, Peters-Golden M. (2003) Extending the understanding of leukotrienes in asthma. Curr Opin Allergy Clin Immunol. 3, 57–63.

    CAS  PubMed  Google Scholar 

  85. Corrigan C, Mallett K, Ying S, et al. (2005) Expression of the cysteinyl leukotriene receptors cysLT(1) and cysLT(2) in aspirin-sensitive and aspirin-tolerant chronic rhinosinusitis. J Allergy Clin Immunol. 115, 316–322.

    CAS  PubMed  Google Scholar 

  86. Fukai H, Ogasawara Y, Migita O, et al. (2004) Association between a polymorphism in cysteinyl leukotriene receptor 2 on chromosome 13q14 and atopic asthma. Pharmacogenetics. 14, 683–690.

    CAS  PubMed  Google Scholar 

  87. Hao L, Sayers I, Cakebread JA, et al. (2006) The cysteinyl-leukotriene type 1 receptor polymorphism 927T/C is associated with atopy severity but not with asthma. Clin Exp Allergy. 36, 735–741.

    CAS  PubMed  Google Scholar 

  88. Kim SH, Oh JM, Kim YS, et al. (2006) Cysteinyl leukotriene receptor 1 promoter polymorphism is associated with aspirin-intolerant asthma in males. Clin Exp Allergy. 36, 433–439.

    CAS  PubMed  Google Scholar 

  89. Park JS, Chang HS, Park CS, et al. (2005) Association analysis of cysteinyl-leukotriene receptor 2 (CYSLTR2) polymorphisms with aspirin intolerance in asthmatics. Pharmacogenet Genomics. 15, 483–492.

    CAS  PubMed  Google Scholar 

  90. Pillai SG, Cousens DJ, Barnes AA, et al. (2004) A coding polymorphism in the CYSLT2 receptor with reduced affinity to LTD4 is associated with asthma. Pharmacogenetics. 14, 627–633.

    CAS  PubMed  Google Scholar 

  91. Zhang J, Migita O, Koga M, Shibasaki M, Arinami T, Noguchi E. (2006) Determination of structure and transcriptional regulation of CYSLTR1 and an association study with asthma and rhinitis. Pediatr Allergy Immunol. 17, 242–249.

    PubMed  Google Scholar 

  92. Lima JJ, Zhang S, Grant A, et al. (2006) Influence of leukotriene pathway polymorphisms on response to montelukast in asthma. Am J Respir Crit Care Med. 173, 379–385.

    CAS  PubMed  Google Scholar 

  93. Jampilek J, Dolezal M, Opletalova V, Hartl J. (2006) 5-Lipoxygenase, leukotrienes biosynthesis and potential antileukotrienic agents. Curr Med Chem. 13, 117–129.

    CAS  PubMed  Google Scholar 

  94. Brock TG. (2005) Regulating leukotriene synthesis: the role of nuclear 5-lipoxygenase. J Cell Biochem. 96, 1203–1211.

    CAS  PubMed  Google Scholar 

  95. Sayers I, Barton S, Rorke S, et al. (2003) Promoter polymorphism in the 5-lipoxygenase (ALOX5) and 5-lipoxygenase-activating protein (ALOX5AP) genes and asthma susceptibility in a Caucasian population. Clin Exp Allergy. 33, 1103–1110.

    CAS  PubMed  Google Scholar 

  96. Zhang WL, Yang XM, Shi J, Sun K, Hui RT. (2006) Polymorphism of SG13S114T/A in the ALOX5AP gene and the risk for stroke in a large Chinese cohort. Yi Chuan Xue Bao. 33, 678–684.

    CAS  PubMed  Google Scholar 

  97. Manev H, Manev R. (2006) 5-Lipoxygenase (ALOX5) and FLAP (ALOX5AP) gene polymorphisms as factors in vascular pathology and Alzheimer's disease. Med Hypotheses. 66, 501–503.

    CAS  PubMed  Google Scholar 

  98. Kaaman M, Ryden M, Axelsson T, et al. (2006) ALOX5AP expression, but not gene haplotypes, is associated with obesity and insulin resistance. Int J Obes (Lond). 30, 447–452.

    CAS  Google Scholar 

  99. Kedda MA, Worsley P, Shi J, Phelps S, Duffy D, Thompson PJ. (2005) Polymorphisms in the 5-lipoxygenase activating protein (ALOX5AP) gene are not associated with asthma in an Australian population. Clin Exp Allergy. 35, 332–338.

    CAS  PubMed  Google Scholar 

  100. Lohmussaar E, Gschwendtner A, Mueller JC, et al. (2005) ALOX5AP gene and the PDE4D gene in a central European population of stroke patients. Stroke. 36, 731–736.

    CAS  PubMed  Google Scholar 

  101. Ben-Asher E, Lancet D. (2004) 5-Lipoxygenase activating protein (ALOX5AP): association with cardiovascular infarction and stroke. Isr Med Assoc J. 6, 318–319.

    PubMed  Google Scholar 

  102. Visvikis-Siest S, Marteau JB. (2006) Genetic variants predisposing to cardiovascular disease. Curr Opin Lipidol. 17, 139–151.

    CAS  PubMed  Google Scholar 

  103. Kim SH, Park HS. (2006) Genetic markers for differentiating aspirin-hypersensitivity. Yonsei Med J. 47, 15–21.

    CAS  PubMed  Google Scholar 

  104. Kim SH, Choi JH, Holloway JW, et al. (2005) Leukotriene-related gene polymorphisms in patients with aspirin-intolerant urticaria and aspirin-intolerant asthma: differing contributions of ALOX5 polymorphism in Korean population. J Korean Med Sci. 20, 926–931.

    CAS  PubMed  Google Scholar 

  105. Kim SH, Bae JS, Suh CH, Nahm DH, Holloway JW, Park HS. (2005) Polymorphism of tandem repeat in promoter of 5-lipoxygenase in ASA-intolerant asthma: a positive association with airway hyperresponsiveness. Allergy. 60, 760–765.

    CAS  PubMed  Google Scholar 

  106. Kim SH, Ye YM, Lee SK, Park HS. (2006) Genetic mechanism of aspirin-induced urticaria/ angioedema. Curr Opin Allergy Clin Immunol. 6, 266–270.

    CAS  PubMed  Google Scholar 

  107. Poole EM, Bigler J, Whitton J, Sibert JG, Potter JD, Ulrich CM. (2006) Prostacyclin synthase and arachidonate 5-lipoxygenase polymorphisms and risk of colorectal polyps. Cancer Epidemiol Biomarkers Prev. 15, 502–508.

    CAS  PubMed  Google Scholar 

  108. Kalayci O, Birben E, Sackesen C, et al. (2006) ALOX5 promoter genotype, asthma severity and LTC production by eosinophils. Allergy. 61, 97–103.

    CAS  PubMed  Google Scholar 

  109. Goodman JE, Bowman ED, Chanock SJ, Alberg AJ, Harris CC. (2004) Arachidonate lipoxygenase (ALOX) and cyclooxygenase (COX) polymorphisms and colon cancer risk. Carcinogenesis. 25, 2467–2472.

    CAS  PubMed  Google Scholar 

  110. Choi JH, Park HS, Oh HB, et al. (2004) Leukotriene-related gene polymorphisms in ASA-intolerant asthma: an association with a haplotype of 5-lipoxygenase. Hum Genet. 114, 337–344.

    CAS  PubMed  Google Scholar 

  111. Samuelsson B, Hoshiko S, Radmark O. (1991) Characterization of the promoter of the human 5-lipoxygenase gene. Adv Prostaglandin Thromboxane Leukot Res. 21A, 1–8.

    CAS  PubMed  Google Scholar 

  112. Hoshiko S, Radmark O, Samuelsson B. (1990) Characterization of the human 5-lipoxygenase gene promoter. Proc Natl Acad Sci U S A. 87, 9073–9077.

    CAS  PubMed  Google Scholar 

  113. In KH, Silverman ES, Asano K, et al. (1999) Mutations in the human 5-lipoxygenase gene. Clin Rev Allergy Immunol. 17, 59–69.

    CAS  PubMed  Google Scholar 

  114. In KH, Asano K, Beier D, et al. (1997) Naturally occurring mutations in the human 5lipoxygenase gene promoter that modify transcription factor binding and reporter gene transcription. J Clin Invest. 99, 1130–1137.

    CAS  PubMed  Google Scholar 

  115. Currie GP, Lima JJ, Sylvester JE, Lee DK, Cockburn WJ, Lipworth BJ. (2003) Leukotriene C4 synthase polymorphisms and responsiveness to leukotriene antagonists in asthma. Br J Clin Pharmacol. 56, 422–426.

    CAS  PubMed  Google Scholar 

  116. Isidoro-Garcia M, Davila I, Moreno E, Lorente F, Gonzalez-Sarmiento R. (2005) Analysis of the leukotriene C4 synthase A-444C promoter polymorphism in a Spanish population. J Allergy Clin Immunol. 115, 206–207.

    PubMed  Google Scholar 

  117. Kawagishi Y, Mita H, Taniguchi M, et al. (2002) Leukotriene C4 synthase promoter polymorphism in Japanese patients with aspirin-induced asthma. J Allergy Clin Immunol. 109, 936–942.

    CAS  PubMed  Google Scholar 

  118. Sanak M, Simon HU, Szczeklik A. (1997) Leukotriene C4 synthase promoter polymorphism and risk of aspirin-induced asthma. Lancet. 350, 1599–1600.

    CAS  PubMed  Google Scholar 

  119. Sanak M, Pierzchalska M, Bazan-Socha S, Szczeklik A. (2000) Enhanced expression of the leukotriene C(4) synthase due to overactive transcription of an allelic variant associated with aspirin-intolerant asthma. Am J Respir Cell Mol Biol. 23, 290–296.

    CAS  PubMed  Google Scholar 

  120. Sanak M, Szczeklik A. (2001) Leukotriene C4 synthase polymorphism and aspirin-induced asthma. J Allergy Clin Immunol. 107, 561–562.

    CAS  PubMed  Google Scholar 

  121. Van SR, Stevenson DD, Baldasaro M, et al. (2000) 5 Flanking region polymorphism of the gene encoding leukotriene C4 synthase does not correlate with the aspirin-intolerant asthma phenotype in the United States. J Allergy Clin Immunol. 106(1 pt. 1), 72–76.

    Google Scholar 

  122. Sampson AP, Cowburn AS, Sladek K, et al. (1997) Profound overexpression of leukotriene C4 synthase in bronchial biopsies from aspirin-intolerant asthmatic patients. Int Arch Allergy Immunol. 113, 355–357.

    CAS  PubMed  Google Scholar 

  123. Barnes PJ. (2006) Corticosteroids: the drugs to beat. Eur J Pharmacol. 533, 2–14.

    CAS  PubMed  Google Scholar 

  124. Pratt WB, Toft DO. (1997) Steroid receptor interactions with heat shock protein and immunophilin chaperones. Endocr Rev. 18, 306–360.

    CAS  PubMed  Google Scholar 

  125. Pratt WB, Gehring U, Toft DO. (1996) Molecular chaperoning of steroid hormone receptors. EXS. 77, 79–95.

    CAS  PubMed  Google Scholar 

  126. Pratt WB, Morishima Y, Murphy M, Harrell M. (2006) Chaperoning of glucocorticoid receptors. Handb Exp Pharmacol. (172), 111–138.

    Google Scholar 

  127. Chen S, Prapapanich V, Rimerman RA, Honore B, Smith DF. (1996) Interactions of p60, a mediator of progesterone receptor assembly, with heat shock proteins hsp90 and hsp70. Mol Endocrinol. 10, 682–693.

    CAS  PubMed  Google Scholar 

  128. Chen S, Smith DF. (1998) Hop as an adaptor in the heat shock protein 70 (hsp70) and hsp90 chaperone machinery. J Biol Chem. 273, 35194–35200.

    CAS  PubMed  Google Scholar 

  129. Dittmar KD, Hutchison KA, Owens-Grillo JK, Pratt WB. (1996) Reconstitution of the steroid receptor.hsp90 heterocomplex assembly system of rabbit reticulocyte lysate. J Biol Chem. 271, 12833–12839.

    CAS  PubMed  Google Scholar 

  130. Dittmar KD, Banach M, Galigniana MD, Pratt WB. (1998) The role of DNAJ-like proteins in glucocorticoid receptor.hsp90 heterocomplex assembly by the reconstituted hsp90.p60. hsp70 foldosome complex. J Biol Chem. 273, 7358–7366.

    CAS  PubMed  Google Scholar 

  131. Grenert JP, Sullivan WP, Fadden P, et al. (1997) The amino-terminal domain of heat shock protein 90 (hsp90) that binds geldanamycin is an ATP/ADP switch domain that regulates hsp90 conformation. J Biol Chem. 272, 23843–23850.

    CAS  PubMed  Google Scholar 

  132. Johnson BD, Schumacher RJ, Ross ED, Toft DO. (1998) Hop modulates Hsp70/Hsp90 interactions in protein folding. J Biol Chem. 273, 3679–3686.

    CAS  PubMed  Google Scholar 

  133. Mendel DB, Orti E. (1988) Isoform composition and stoichiometry of the approx 90-kDa heat shock protein associated with glucocorticoid receptors. J Biol Chem. 263, 6695–6702.

    CAS  PubMed  Google Scholar 

  134. Minami Y, Kimura Y, Kawasaki H, Suzuki K, Yahara I. (1994) The carboxy-terminal region of mammalian HSP90 is required for its dimerization and function in vivo. Mol Cell Biol. 14, 1459–1464.

    CAS  PubMed  Google Scholar 

  135. Pratt WB, Silverstein AM, Galigniana MD. (1999) A model for the cytoplasmic trafficking of signalling proteins involving the hsp90-binding immunophilins and p50cdc37. Cell Signal. 11, 839–851.

    CAS  PubMed  Google Scholar 

  136. Pratt WB, Galigniana MD, Harrell JM, DeFranco DB. (2004) Role of hsp90 and the hsp90binding immunophilins in signalling protein movement. Cell Signal. 16, 857–872.

    CAS  PubMed  Google Scholar 

  137. Rogatsky I, Ivashkiv LB. (2006) Glucocorticoid modulation of cytokine signaling. Tissue Antigens. 68, 1–12.

    CAS  PubMed  Google Scholar 

  138. Geserick C, Meyer HA, Haendler B. (2005) The role of DNA response elements as allosteric modulators of steroid receptor function. Mol Cell Endocrinol. 236, 1–7.

    CAS  PubMed  Google Scholar 

  139. Cato AC, Schacke H, Sterry W, Asadullah K. (2004) The glucocorticoid receptor as target for classic and novel anti-inflammatory therapy. Curr Drug Targets Inflamm Allergy. 3, 347–353.

    CAS  PubMed  Google Scholar 

  140. Schoneveld OJ, Gaemers IC, Lamers WH. (2004) Mechanisms of glucocorticoid signalling. Biochim Biophys Acta. 1680, 114–128.

    CAS  PubMed  Google Scholar 

  141. Hayashi R, Wada H, Ito K, Adcock IM. Effects of glucocorticoids on gene transcription. Eur J Pharmacol 500, 51–62.

    Google Scholar 

  142. Breslin MB, Geng CD, Vedeckis WV. (2001) Multiple promoters exist in the human GR gene, one of which is activated by glucocorticoids. Mol Endocrinol. 15, 1381–1395.

    CAS  PubMed  Google Scholar 

  143. Encio IJ, Detera-Wadleigh SD. (1991) The genomic structure of the human glucocorticoid receptor. J Biol Chem. 266, 7182–7188.

    CAS  PubMed  Google Scholar 

  144. Francke U, Foellmer BE. (1989) The glucocorticoid receptor gene is in 5q31–q32. Genomics 4, 610–612.

    CAS  PubMed  Google Scholar 

  145. Gehring U. (1993) The structure of glucocorticoid receptors. J Steroid Biochem Mol Biol. 45, 183–190.

    CAS  PubMed  Google Scholar 

  146. Nunez BS, Vedeckis WV. (2002) Characterization of promoter 1B in the human glucocorticoid receptor gene. Mol Cell Endocrinol. 189, 191–199.

    CAS  PubMed  Google Scholar 

  147. Rivers C, Levy A, Hancock J, Lightman S, Norman M. (1999) Insertion of an amino acid in the DNA-binding domain of the glucocorticoid receptor as a result of alternative splicing. J Clin Endocrinol Metab. 84, 4283–4286.

    CAS  PubMed  Google Scholar 

  148. Oakley RH, Sar M, Cidlowski JA. (1996) The human glucocorticoid receptor beta isoform. Expression, biochemical properties, and putative function. J Biol Chem. 271, 9550–9559.

    CAS  PubMed  Google Scholar 

  149. Leung DY, Hamid Q, Vottero A, et al. (1997) Association of glucocorticoid insensitivity with increased expression of glucocorticoid receptor beta. J Exp Med. 186, 1567–1574.

    CAS  PubMed  Google Scholar 

  150. Christodoulopoulos P, Leung DY, Elliott MW, et al. (2000) Increased number of glucocorticoid receptor-beta-expressing cells in the airways in fatal asthma. J Allergy Clin Immunol. 106, 479–484.

    CAS  PubMed  Google Scholar 

  151. Hamid QA, Wenzel SE, Hauk PJ, et al. (1999) Increased glucocorticoid receptor beta in airway cells of glucocorticoid-insensitive asthma. Am J Respir Crit Care Med. 159(5 pt. 1), 1600–1604.

    CAS  PubMed  Google Scholar 

  152. Hauk PJ, Goleva E, Strickland I, et al. (2002) Increased glucocorticoid receptor Beta expression converts mouse hybridoma cells to a corticosteroid-insensitive phenotype. Am J Respir Cell Mol Biol. 27, 361–367.

    CAS  PubMed  Google Scholar 

  153. Sousa AR, Lane SJ, Cidlowski JA, Staynov DZ, Lee TH. (2000) Glucocorticoid resistance in asthma is associated with elevated in vivo expression of the glucocorticoid receptor beta-iso-form. J Allergy Clin Immunol. 105, 943–950.

    CAS  PubMed  Google Scholar 

  154. Lewis-Tuffin LJ, Cidlowski JA. (2006) The physiology of human glucocorticoid receptor beta (hGRbeta) and glucocorticoid resistance. Ann N Y Acad Sci. 1069, 1–9.

    CAS  PubMed  Google Scholar 

  155. Bergeron C, Fukakusa M, Olivenstein R, et al. (2006) Increased glucocorticoid receptor-beta expression, but not decreased histone deacetylase 2, in severe asthma. J Allergy Clin Immunol. 117, 703–705.

    CAS  PubMed  Google Scholar 

  156. Goleva E, Li LB, Eves PT, Strand MJ, Martin RJ, Leung DY. (2006) Increased glucocorticoid receptor beta alters steroid response in glucocorticoid-insensitive asthma. Am J Respir Crit Care Med. 173, 607–616.

    CAS  PubMed  Google Scholar 

  157. Rivers C, Levy A, Hancock J, Lightman S, Norman M. (1999) Insertion of an amino acid in the DNA-binding domain of the glucocorticoid receptor as a result of alternative splicing. J Clin Endocrinol Metab. 84, 4283–4286.

    CAS  PubMed  Google Scholar 

  158. Hurley DM, Accili D, Stratakis CA, et al. (1991) Point mutation causing a single amino acid substitution in the hormone binding domain of the glucocorticoid receptor in familial glucocorticoid resistance. J Clin Invest. 87, 680–686.

    CAS  PubMed  Google Scholar 

  159. Karl M, Lamberts SW, Detera-Wadleigh SD, et al. (1993) Familial glucocorticoid resistance caused by a splice site deletion in the human glucocorticoid receptor gene. J Clin Endocrinol Metab. 76, 683–689.

    CAS  PubMed  Google Scholar 

  160. Karl M, Lamberts SW, Koper JW, et al. (1996) Cushing's disease preceded by generalized glucocorticoid resistance: clinical consequences of a novel, dominant-negative glucocorticoid receptor mutation. Proc Assoc Am Physicians. 108, 296–307.

    CAS  PubMed  Google Scholar 

  161. Karl M, Von Wichert G, Kempter E, et al. (1996) Nelson's syndrome associated with a somatic frame shift mutation in the glucocorticoid receptor gene. J Clin Endocrinol Metab. 81, 124–129.

    CAS  PubMed  Google Scholar 

  162. Malchoff DM, Brufsky A, Reardon G, et al. (1993) A mutation of the glucocorticoid receptor in primary cortisol resistance. J Clin Invest. 91, 1918–1925.

    CAS  PubMed  Google Scholar 

  163. Mendonca BB, Leite MV, de Castro M, et al. (2002) Female pseudohermaphroditism caused by a novel homozygous missense mutation of the GR gene. J Clin Endocrinol Metab. 87, 1805–1809.

    CAS  PubMed  Google Scholar 

  164. Ruiz M, Lind U, Gafvels M, et al. (2001) Characterization of two novel mutations in the glucocorticoid receptor gene in patients with primary cortisol resistance. Clin Endocrinol (Oxf). 55, 363–371.

    CAS  Google Scholar 

  165. Strasser-Wozak EM, Hattmannstorfer R, Hala M, et al. (1995) Splice site mutation in the glucocorticoid receptor gene causes resistance to glucocorticoid-induced apoptosis in a human acute leukemic cell line. Cancer Res. 55, 348–353.

    CAS  PubMed  Google Scholar 

  166. Vottero A, Kino T, Combe H, Lecomte P, Chrousos GP. (2002) A novel, C-terminal dominant negative mutation of the GR causes familial glucocorticoid resistance through abnormal interactions with p160 steroid receptor coactivators. J Clin Endocrinol Metab. 87, 2658–2667.

    CAS  PubMed  Google Scholar 

  167. Majnik J, Patocs A, Balogh K, Toth M, Racz K. (2004) A rapid and simple method for detection of Asn363Ser polymorphism of the human glucocorticoid receptor gene. J Steroid Biochem Mol Biol. 92, 465–468.

    CAS  PubMed  Google Scholar 

  168. Syed AA, Irving JA, Redfern CP, et al. (2004) Low prevalence of the N363S polymorphism of the glucocorticoid receptor in South Asians living in the United Kingdom. J Clin Endocrinol Metab. 89, 232–235.

    CAS  PubMed  Google Scholar 

  169. Lei SF, Deng FY, Liu XH, et al. (2003) Polymorphisms of four bone mineral density candidate genes in Chinese populations and comparison with other populations of different ethnicity. J Bone Miner Metab. 21, 34–42.

    CAS  PubMed  Google Scholar 

  170. Echwald SM, Sorensen TI, Andersen T, Pedersen O. (2001) The Asn363Ser variant of the glucocorticoid receptor gene is not associated with obesity or weight gain in Danish men. Int J Obes Relat Metab Disord. 25, 1563–1565.

    CAS  PubMed  Google Scholar 

  171. DeRijk R, de Kloet ER. (2005) Corticosteroid receptor genetic polymorphisms and stress responsivity. Endocrine. 28, 263–270.

    CAS  PubMed  Google Scholar 

  172. Huizenga NA, Koper JW, De Lange P, et al. (1998) A polymorphism in the glucocorticoid receptor gene may be associated with and increased sensitivity to glucocorticoids in vivo. J Clin Endocrinol Metab. 83, 144–151.

    CAS  PubMed  Google Scholar 

  173. Schaaf MJ, Cidlowski JA. (2002) AUUUA motifs in the 3′UTR of human glucocorticoid receptor alpha and beta mRNA destabilize mRNA and decrease receptor protein expression. Steroids. 67, 627–636.

    CAS  PubMed  Google Scholar 

  174. Tantisira KG, Lake S, Silverman ES, et al. (2004) Corticosteroid pharmacogenetics: association of sequence variants in CRHR1 with improved lung function in asthmatics treated with inhaled corticosteroids. Hum Mol Genet. 13, 1353–1359.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2008 Humana Press, a part of Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Hawkins, G.A., Peters, S.P. (2008). Pharmacogenetics of Asthma. In: Yan, Q. (eds) Pharmacogenomics in Drug Discovery and Development. Methods in Molecular Biology™, vol 448. Humana Press. https://doi.org/10.1007/978-1-59745-205-2_11

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-205-2_11

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-887-4

  • Online ISBN: 978-1-59745-205-2

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics