Pharmacogenomics of asthma

Current Pharmaceutical Design

Volumn 12, Issue 25, 2006, Pages 3195-3206

  Pahl, Andreas ^a   Benediktus, Ewald ^a   Chialda, Ligia ^a  

^a UNIVERSITY OF ERLANGEN NUREMBERG   (Germany)

Author keywords

Asthma; Pharmacogenomics

Indexed keywords

ACETYLSALICYLIC ACID; AMINO ACID TRANSPORTER; ANTIASTHMATIC AGENT; ARACHIDONATE 5 LIPOXYGENASE; ARACHIDONIC ACID; ARGINASE; ARGININE; BETA 2 ADRENERGIC RECEPTOR; BETA 2 ADRENERGIC RECEPTOR STIMULATING AGENT; BETA ARRESTIN; CORTICOSTEROID; FORMOTEROL; G PROTEIN COUPLED RECEPTOR KINASE 2; GLUCOCORTICOID; GLUCOCORTICOID RECEPTOR; GLUTAMIC ACID; GLUTAMINE; GLYCINE; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; IMMUNOGLOBULIN E; INTERLEUKIN 13; INTERLEUKIN 3; INTERLEUKIN 4; INTERLEUKIN 5; INTERLEUKIN 9; LEUKOTRIENE C4 SYNTHASE; PLACEBO; PROSTAGLANDIN SYNTHASE; SALBUTAMOL;

AFRICAN AMERICAN; AMINO ACID SUBSTITUTION; ASTHMA; CAUCASIAN; CELL MATURATION; CELL PROLIFERATION; CHROMOSOME 5Q; DESENSITIZATION; DRUG CHOICE; DRUG DISPOSITION; DRUG EFFECT; EOSINOPHIL; GENE ACTIVITY; GENE EXPRESSION; GENE EXPRESSION PROFILING; GENE FREQUENCY; GENE LINKAGE DISEQUILIBRIUM; GENE MAPPING; GENETIC ANALYSIS; GENETIC POLYMORPHISM; GENETIC TRANSFECTION; GENETIC VARIABILITY; HUMAN; IMMUNOGLOBULIN PRODUCTION; IN VITRO STUDY; INHERITANCE; LYMPHOCYTE; MAST CELL; MICROARRAY ANALYSIS; MONKEY; MOUSE; NONHUMAN; PHARMACOGENOMICS; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN FAMILY; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; RACE DIFFERENCE; RECEPTOR BINDING; REVIEW; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; SPECIES DIFFERENCE; TACHYPHYLAXIS; TREATMENT OUTCOME; TREATMENT RESPONSE;

ANIMALS; ANTI-ASTHMATIC AGENTS; ASTHMA; HUMANS; PHARMACOGENETICS; POLYMORPHISM, GENETIC;

EID: 33748521551     PISSN: 13816128     EISSN: None     Source Type: Journal    
DOI: 10.2174/138161206778194105     Document Type: Review

References (109)

1. Szefler SJ, Martin RJ, King TS, Boushey HA, Cherniack RM, Chinchilli VM, et al. Significant variability in response to inhaled corticosteroids for persistent asthma. J Allergy Clin Immunol 2002; 109(3): 410-418.
2. Ingelman-Sundberg M. Pharmacogenetics of cytochrome P450 and its applications in drug therapy: the past, present and future. Trends Pharmacol Sci 2004; 25(4): 193-200.
3. Palmer LJ, Silverman ES, Weiss ST, Drazen JM. Pharmacogenetics of asthma. Am J Respir Crit Care Med 2002; 165(7): 861-866.
4. Steinke JW, Borish L, Rosenwasser LJ. 5. Genetics of hypersensitivity. J Allergy Clin Immunol 2003; 111(2 Suppl): S495-501.
5. Liggett SB. Polymorphisms of adrenergic receptors: variations on a theme. Assay Drug Dev Technol 2003; 1(2): 317-326.
6. Liggett SB. Update on current concepts of the molecular basis of beta2-adrenergic receptor signaling. J Allergy Clin Immunol 2002; 110(6 Suppl): S223-227.
7. Reihsaus E, Innis M, MacIntyre N, Liggett SB. Mutations in the gene encoding for the beta 2-adrenergic receptor in normal and asthmatic subjects. Am J Respir Cell Mol Biol 1993; 8(3): 334-339.
8. Kirstein SL, Insel PA. Autonomic nervous system pharmacogenomics: a progress report. Pharmacol Rev 2004; 56(1): 31-52.
9. Fu J, Chen H, Hu L, Zhang H, Ma Y, Chen Y. Association between the genetic polymorphisms of beta2-adrenergic receptor gene and the asthma susceptibility and clinical phenotypes in a Chinese population. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 2002; 19(1): 41-45.
10. Green SA, Turki J, Innis M, Liggett SB. Amino-terminal polymorphisms of the human beta 2-adrenergic receptor impart distinct agonist-promoted regulatory properties. Biochemistry 1994; 33(32): 9414-9419.
11. Moore PE, Laporte JD, Abraham JH, Schwartzman IN, Yandava CN, Silverman ES, et al. Polymorphism of the beta(2)-adrenergic receptor gene and desensitization in human airway smooth muscle. Am J Respir Crit Care Med 2000; 162(6): 2117-2124.
12. Makimoto H, Sakaeda T, Nishiguchi K, Kita T, Sakai T, Komada F, et al. Beta2-adrenergic receptor genotype-related changes in cAMP levels in peripheral blood mononuclear cells after multiple-dose oral procaterol. Pharm Res 2001; 18(12): 1651-1654.
13. Buscher R, Eilmes KJ, Grasemann H, Torres B, Knauer N, Sroka K, et al. Beta2 adrenoceptor gene polymorphisms in cystic fibrosis lung disease. Pharmacogenetics 2002; 12(5): 347-353.
14. Chong LK, Chowdry J, Ghahramani P, Peachell PT. Influence of genetic polymorphisms in the beta2-adrenoceptor on desensitization in human lung mast cells. Pharmacogenetics 2000; 10(2): 153-162.
15. Lipworth B, Koppelman GH, Wheatley AP, Le Jeune I, Coutie W, Meurs H, et al. Beta2 adrenoceptor promoter polymorphisms: extended haplotypes and functional effects in peripheral blood mononuclear cells. Thorax 2002; 57(1): 61-66.
16. Lipworth BJ, Hall IP, Aziz I, Tan KS, Wheatley A. Beta2-adrenoceptor polymorphism and bronchoprotective sensitivity with regular short- and long-acting beta2-agonist therapy. Clin Sci (Lond) 1999; 96(3): 253-259.
17. Green SA, Cole G, Jacinto M, Innis M, Liggett SB. A polymorphism of the human beta 2-adrenergic receptor within the fourth transmembrane domain alters ligand binding and functional properties of the receptor. J Biol Chem 1993; 268(31): 23116-23121.
18. Green SA, Rathz DA, Schuster AJ, Liggett SB. The Ile164 beta(2)-adrenoceptor polymorphism alters salmeterol exosite binding and conventional agonist coupling to G(s). Eur J Pharmacol 2001; 421(3): 141-147.
19. Liggett SB. Pharmacogenetics of beta-1- and beta-2-adrenergic receptors. Pharmacology 2000; 61(3): 167-173.
20. Parola AL, Kobilka BK. The peptide product of a 5′ leader cistron in the beta 2 adrenergic receptor mRNA inhibits receptor synthesis. J Biol Chem 1994; 269(6): 4497-4505.
21. McGraw DW, Donnelly ET, Eason MG, Green SA, Liggett SB. Role of beta ARK in long-term agonist-promoted desensitisation of the beta 2-adrenergic receptor. Cell Signal 1998; 10(3): 197-204.
22. Scott MG, Swan C, Wheatley AP, Hall IP. Identification of novel polymorphisms within the promoter region of the human beta2 adrenergic receptor gene. Br J Pharmacol 1999; 126(4): 841-844.
23. Drysdale CM, McGraw DW, Stack CB, Stephens JC, Judson RS, Nandabalan K, et al. Complex promoter and coding region beta 2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness. Proc Natl Acad Sci USA 2000; 97(19): 10483-10488.
24. Martinez FD, Graves PE, Baldini M, Solomon S, Erickson R. Association between genetic polymorphisms of the beta2-adrenoceptor and response to albuterol in children with and without a history of wheezing. J Clin Invest 1997; 100(12): 3184-3188.
25. Israel E, Drazen JM, Liggett SB, Boushey HA, Cherniack RM, Chinchilli VM, et al. 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 2000; 162(1): 75-80.
26. Israel E, Drazen JM, Liggett SB, Boushey HA, Cherniack RM, Chinchilli VM, et al. Effect of polymorphism of the beta(2)-adrenergic receptor on response to regular use of albuterol in asthma. Int Arch Allergy Immunol 2001; 124(1-3): 183-186.
27. Lee DK, Currie GP, Hall IP, Lima JJ, Lipworth BJ. The arginine-16 beta2-adrenoceptor polymorphism predisposes to bronchoprotective subsensitivity in patients treated with formoterol and salmeterol. Br J Clin Pharmacol 2004; 57(1): 68-75.
28. Barnes PJ, Adcock IM. How do corticosteroids work in asthma? Ann Intern Med 2003; 139(5 Pt 1): 359-370.
29. Suissa S, Ernst P. Inhaled corticosteroids: impact on asthma morbidity and mortality. J Allergy Clin Immunol 2001; 107(6): 937-944.
30. Suissa S, Ernst P, Benayoun S, Baltzan M, Cai B. Low-dose inhaled corticosteroids and the prevention of death from asthma. N Engl J Med 2000; 343(5): 332-336.
31. Barnes PJ, Adcock IM. Transcription factors and asthma. Eur Respir J 1998; 12(1): 221-234.
32. Norman M, Hearing SD. Glucocorticoid resistance - what is known? Curr Opin Pharmacol 2002; 2(6): 723-729.
33. Caramori G, Adcock I. Pharmacology of airway inflammation in asthma and COPD. Pulm Pharmacol Ther 2003; 16(5): 247-277.
34. Leung DY, Bloom JW. Update on glucocorticoid action and resistance. J Allergy Clin Immunol 2003; 111(1): 3-22; quiz 23.
35. Cosio BG, Mann B, Ito K, Jazrawi E, Barnes PJ, Chung KF, et al. Histone acetylase and deacetylase activity in alveolar macrophages and blood mononocytes in asthma. Am J Respir Crit Care Med 2004; 170(2): 141-147.
36. Ito K, Jazrawi E, Cosio B, Barnes PJ, Adcock IM. p65-activated histone acetyltransferase activity is repressed by glucocorticoids: mifepristone fails to recruit HDAC2 to the p65-HAT complex. J Biol Chem 2001; 276(32): 30208-30215.
37. Ito K, Barnes PJ, Adcock IM. Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin-1 beta-induced histone H4 acetylation on lysines 8 and 12. Mol Cell Biol 2000; 20(18): 6891-6903.
38. Lamberts SW, Huizenga AT, de Lange P, de Jong FH, Koper JW. Clinical aspects of glucocorticoid sensitivity. Steroids 1996; 61(4): 157-160.
39. Hearing SD, Norman M, Smyth C, Foy C, Dayan CM. Wide variation in lymphocyte steroid sensitivity among healthy human volunteers. J Clin Endocrinol Metab 1994; 84(11): 4149-4154.
40. Koper JW, Stolk RP, de Lange P, Huizenga NA, Molijn GJ, Pols HA, et al. Lack of association between five polymorphisms in the human glucocorticoid receptor gene and glucocorticoid resistance. Hum Genet 1997; 99(5): 663-668.
41. Lane SJ, Lee TH. Corticosteroid resistance in other disease states and tissues. Am J Respir Crit Care Med 1996; 154(2 Pt 2): S62-65.
42. Hearing SD, Norman M, Probert CS, Haslam N, Dayan CM. Predicting therapeutic outcome in severe ulcerative colitis by measuring in vitro steroid sensitivity of proliferating peripheral blood lymphocytes. Gut 1999; 45(3): 382-388.
43. Barnes PJ, Adcock IM. Steroid resistance in asthma. Qjm 1995; 88(7): 455-468.
44. Adcock IM, Lane SJ. Corticosteroid-insensitive asthma: molecular mechanisms. J Endocrinol 2003; 178(3): 347-355.
45. Chan MT, Leung DY, Szefler SJ, Spahn JD. Difficult-to-control asthma: clinical characteristics of steroid-insensitive asthma. J Allergy Clin Immunol 1998; 101(5): 594-601.
46. van Schaardenburg D, Valkema R, Dijkmans BA, Papapoulos S, Zwinderman AH, Han KH, et al. Prednisone treatment of elderly-onset rheumatoid arthritis. Disease activity and bone mass in comparison with chloroquine treatment. Arthritis Rheum 1995; 38(3): 334-342.
47. Seki M, Ushiyama C, Seta N, Abe K, Fukazawa T, Asakawa J, et al. Apoptosis of lymphocytes induced by glucocorticoids and relationship to therapeutic efficacy in patients with systemic lupus erythematosus. Arthritis Rheum 1998; 41(5): 823-830.
48. Burchard EG, Silverman EK, Rosenwasser LJ, Borish L, Yandava C, Pillari A, et al. Association between a sequence variant in the IL-4 gene promoter and FEV(1) in asthma. Am J Respir Crit Care Med 1999; 160(3): 919-922.
49. Rosa-Rosa L, Zimmermann N, Bernstein JA, Rothenberg ME, Khurana Hershey GK. The R576 IL-4 receptor alpha allele correlates with asthma severity. J Allergy Clin Immunol 1999; 104(5): 1008-1014.
50. Sher ER, Leung DY, Surs W, Kam JC, Zieg G, Kamada AK, et al. Steroid-resistant asthma. Cellular mechanisms contributing to inadequate response to glucocorticoid therapy. J Clin Invest 1994; 93(1): 33-39.
51. Kam JC, Szefler SJ, Surs W, Sher ER, Leung DY. Combination IL-2 and IL-4 reduces glucocorticoid receptor-binding affinity and T cell response to glucocorticoids. J Immunol 1993; 151(7): 3460-3466.
52. Adcock IM, Lane SJ, Brown CR, Peters MJ, Lee TH, Barnes PJ. Differences in binding of glucocorticoid receptor to DNA in steroid-resistant asthma. J Immunol 1995; 154(7): 3500-3505.
53. Adcock IM, Lane SJ, Brown CR, Lee TH, Barnes PJ. Abnormal glucocorticoid receptor-activator protein 1 interaction in steroid-resistant asthma. J Exp Med 1995; 182(6): 1951-1958.
54. Leung DY, Hamid Q, Vottero A, Szefler SJ, Surs W, Minshall E, et al. Association of glucocorticoid insensitivity with increased expression of glucocorticoid receptor beta. J Exp Med 1997; 186(9): 1567-1574.
55. Ito K, Caramori G, Lim S, Oates T, Chung KF, Barnes PJ, et al. Expression and activity of histone deacetylases in human asthmatic airways. Am J Respir Crit Care Med 2002; 166(3): 392-396.
56. Ito K, Lim S, Caramori G, Chung KF, Barnes PJ, Adcock IM. Cigarette smoking reduces histone deacetylase 2 expression, enhances cytokine expression, and inhibits glucocorticoid actions in alveolar macrophages. FASEB J 2001; 15(6): 1110-1112.
57. Matthews JG, Ito K, Barnes PJ, Adcock IM. Defective glucocorticoid receptor nuclear translocation and altered histone acetylation patterns in glucocorticoid-resistant patients. J Allergy Clin Immunol 2004; 113(6): 1100-1108.
58. Chikanza IC, Kozaci D, Chernajovsky Y. The molecular and cellular basis of corticosteroid resistance. J Endocrinol 2003; 179(3): 301-310.
59. Huizenga NA, de Lange P, Koper JW, de Herder WW, Abs R, Kasteren JH, et al. Five patients with biochemical and/or clinical generalized glucocorticoid resistance without alterations in the glucocorticoid receptor gene. J Clin Endocrinol Metab 2000; 85(5): 2076-2081.
60. Bray PJ, Cotton RG. Variations of the human glucocorticoid receptor gene (NR3C1): pathological and in vitro mutations and polymorphisms. Hum Mutat 2003; 21(6): 557-568.
61. Stevens A, Ray DW, Zeggini E, John S, Richards HL, Griffiths CE, et al. Glucocorticoid sensitivity is determined by a specific glucocorticoid receptor haplotype. J Clin Endocrinol Metab 2004; 89(2): 892-897.
62. DeRijk RH, Schaaf M, de Kloet ER. Glucocorticoid receptor variants: clinical implications. J Steroid Biochem. Mol Biol 2002; 81(2): 103-122.
63. Tantisira KG, Lake S, Silverman ES, Palmer LJ, Lazarus R, Silverman EK, et al. Corticosteroid pharmacogenetics: association of sequence variants in CRHR1 with improved lung function in asthmatics treated with inhaled corticosteroids. Hum Mol Genet 2004; 13(13): 1353-1359.
64. Babu KS, Salvi SS. Aspirin and asthma. Chest 2000; 118(5): 1470-1476.
65. Szczeklik A. The cyclooxygenase theory of aspirin-induced asthma. Eur Respir J 1990; 3(5): 588-593.
66. Jawien J. A new insight into aspirin-induced asthma. Eur J Clin Invest 2002; 32(2): 134-138.
67. Szczeklik A, Stevenson DD. Aspirin-induced asthma: advances in pathogenesis, diagnosis, and management. J Allergy Clin Immunol 2003; 111(5): 913-921; quiz 922.
68. Szczeklik A. Aspirin-induced asthma as a viral disease. Clin Allergy 1988; 18(1): 15-20.
69. Sanak M, Szczeklik A. Genetics of aspirin induced asthma. Thorax 2000; 55(Suppl 2): S45-47.
70. Pavord ID, Tattersfield AE. Bronchoprotective role for endogenous prostaglandin E2. Lancet 1995; 345(8947): 436-438.
71. Kowalski ML, Sliwinska-Kowalska M, Igarashi Y, White MV, Wojciechowska B, Brayton P, et al. Nasal secretions in response to acetylsalicylic acid. J Allergy Clin Immunol 1993; 91(2): 580-598.
72. Daffern PJ, Muilenburg D, Hugli TE, Stevenson DD. Association of urinary leukotriene E4 excretion during aspirin challenges with severity of respiratory responses. J Allergy Clin Immunol 1999; 104(3 Pt 1): 559-564.
73. Cowburn AS, Sladek K, Soja J, Adamek L, Nizankowska E, Szczeklik A, et al. Overexpression of leukotriene C4 synthase in bronchial biopsies from patients with aspirin-intolerant asthma. J Clin Invest 1998; 101(4): 834-846.
74. Sousa AR, Lams BE, Pfister R, Christie PE, Schmitz M, Lee TH. Expression of interleukin-5 and granulocyte-macrophage colony-stimulating factor in aspirin-sensitive and non-aspirin-sensitive asthmatic airways. Am J Respir Crit Care Med 1997; 156(5): 1384-1389.
75. Sanak M, Simon HU, Szczeklik A. Leukotriene C4 synthase promoter polymorphism and risk of aspirin-induced asthma. Lancet 1997; 350(9091): 1599-1600.
76. Sanak M, Pierzchalska M, Bazan-Socha S, Szczeklik A. 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 2000; 23(3): 290-296.
77. Szczeklik A, Sanak M. Genetic mechanisms in aspirin-induced asthma. Am J Respir Crit Care Med 2000; 161(2 Pt 2): S142-146.
78. Torres-Galvan MJ, Ortega N, Sanchez-Garcia F, Blanco C, Carrillo T, Quiralte J. LTC4-synthase A-444C polymorphism: lack of association with NSAID-induced isolated periorbital angioedema in a Spanish population. Ann Allergy Asthma Immunol 2001; 87(6): 506-510.
79. Van Sambeek R, Stevenson DD, Baldasaro M, Lam BK, Zhao J, Yoshida S, et al. 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 2000; 106(1 Pt 1): 72-76.
80. Sayers I, Barton S, Rorke S, Sawyer J, Peng Q, Beghe B, 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(8): 1103-1110.
81. Israel E, Fischer AR, Rosenberg MA, Lilly CM, Callery JC, Shapiro J, et al. The pivotal role of 5-lipoxygenase products in the reaction of aspirin-sensitive asthmatics to aspirin. Am Rev Respir Dis 1993; 148(6 Pt 1): 1447-1451.
82. Werz O. 5-lipoxygenase: cellular biology and molecular pharmacology. Curr Drug Targets Inflamm Allergy 2002; 1(1): 23-44.
83. Funk CD, Hoshiko S, Matsumoto T, Rdmark O, Samuelsson B. Characterization of the human 5-lipoxygenase gene. Proc Natl Acad Sci USA 1989; 86(8): 2587-2591.
84. Murakami M, Austen KF, Bingham CO 3rd, Friend DS, Penrose JF, Arm JP. Interleukin-3 regulates development of the 5-lipoxygenase/leukotriene C4 synthase pathway in mouse mast cells. J Biol Chem 1995; 270(39): 22653-22656.
85. Hoshiko S, Radmark O, Samuelsson B. Characterization of the human 5-lipoxygenase gene promoter. Proc Natl Acad Sci USA 1990; 87(23): 9073-9077.
86. In KH, Asano K, Beier D, Grobholz J, Finn PW, Silverman EK, et al. Naturally occurring mutations in the human 5-lipoxygenase gene promoter that modify transcription factor binding and reporter gene transcription. J Clin Invest 1997; 99(5): 1130-1137.
87. Drazen JM, Silverman ES. Genetic determinants of 5-lipoxygenase transcription. Int Arch Allergy Immunol 1999; 118(24): 275-278.
88. Silverman ES, Du J, De Sanctis GT, Radmark O, Samuelsson B, Drazen JM, et al. Egr-1 and Sp1 interact functionally with the 5-lipoxygenase promoter and its naturally occurring mutants. Am J Respir Cell Mol Biol 1998; 19(2): 316-323.
89. Drazen JM, Yandava CN, Dube L, Szczerback N, Hippensteel R, Pillari A, et al. Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment. Nat Genet 1999; 22(2): 168-170.
90. Laprise C, Sladek R, Ponton A, Bernier MC, Hudson TJ, Laviolette M. Functional classes of bronchial mucosa genes that are differentially expressed in asthma. BMC Genomics 2004; 5(1): 21.
91. Brutsche MH, Brutsche IC, Wood P, Brass A, Morrison N, Rattay M, et al. Apoptosis signals in atopy and asthma measured with cDNA arrays. Clin Exp Immunol 2001; 123(2): 181-187.
92. Brutsche MH, Joos L, Carlen Brutsche IE, Bissinger R, Tamm M, Custovic A, et al. Array-based diagnostic gene-expression score for atopy and asthma. J Allergy Clin Immunol 2002; 109(2): 271-273.
93. Zimmermann N, King NE, Laporte J, Yang M, Mishra A, Pope SM, et al. Dissection of experimental asthma with DNA microarray analysis identifies arginase in asthma pathogenesis. J Clin Invest 2003; 111(12): 1863-1874.
94. Zimmermann N, Mishra A, King NE, Fulkerson PC, Doepker MP, Nikolaidis NM, et al. Transcript signatures in experimental asthma: identification of STAT6-dependent and -independent pathways. J Immunol 2004; 172(3): 1815-1824.
95. Zou J, Young S, Zhu F, Gheyas F, Skeans S, Wan Y, et al. Microarray profile of differentially expressed genes in a monkey model of allergic asthma. Genome Biol 2002; 3(5): research0020.
96. Darvasi A. Experimental strategies for the genetic dissection of complex traits in animal models. Nat Genet 1998; 18(1): 19-24.
97. Taylor DR, Drazen JM, Herbison GP, Yandava CN, Hancox RJ, Town GI. Asthma exacerbations during long term beta agonist use: influence of beta(2) adrenoceptor polymorphism. Thorax 2000; 55(9): 762-767.
98. Lee DK, Bates CE, Lipworth BJ. Acute systemic effects of inhaled salbutamol in asthmatic subjects expressing common homozygous beta2-adrenoceptor haplotypes at positions 16 and 27. Br J Clin Pharmacol 2004; 57(1): 100-104.
99. Tan S, Hall IP, Dewar J, Dow E, Lipworth B. Association between beta 2-adrenoceptor polymorphism and susceptibility to bronchodilator desensitisation in moderately severe stable asthmatics. Lancet 1997; 350(9083): 995-999.
100. Kotani Y, Nishimura Y, Maeda H, Yokoyama M. Beta2-adrenergic receptor polymorphisms affect airway responsiveness to salbutamol in asthmatics. J Asthma 1999; 36(7): 583-590.
101. Aziz I, Lipworth BJ. In vivo effect of albuterol on methacholine-contracted bronchi in conjunction with salmeterol and formoterol. J Allergy Clin Immunol 1999; 103(5 Pt 1): 816-822.
102. Lima JJ, Thomason DB, Mohamed MH, Eberle LV, Self TH, Johnson JA. Impact of genetic polymorphisms of the beta2-adrenergic receptor on albuterol bronchodilator pharmacodynamics. Clin Pharmacol Ther 1999; 65(5): 519-525.
103. Lima JJ, Mohamed MH, Self TH, Eberle LV, Johnson JA. Importance of beta(2)adrenergic receptor genotype, gender and race on albuterol-evoked bronchodilation in asthmatics. Pulm Pharmacol Ther 2000; 13(3): 127-134.
104. Hancox RJ, Sears MR, Taylor DR. Polymorphism of the beta2-adrenoceptor and the response to long-term beta2-agonist therapy in asthma. Eur Respir J 1998; 11(3): 589-593.
105. Lipworth BJ, Hall IP, Tan S, Aziz I, Coutie W. Effects of genetic polymorphism on ex vivo and in vivo function of beta2-adrenoceptors in asthmatic patients. Chest 1999; 115(2): 324-328.
106. Lipworth BJ, Dempsey OJ, Aziz I. Functional antagonism with formoterol and salmeterol in asthmatic patients expressing the homozygous glycine-16 beta(2)-adrenoceptor polymorphism. Chest 2000; 118(2): 321-328.
107. Bazan-Socha S, Bukiej A, Marcinkiewicz C, Musial J. Integrins in pulmonary inflammatory diseases. Curr Pharm Des 2005; 11(7): 893-901.
108. Berenguer B, La Casa C, de la Matta MJ, Martin-Calero MJ. Pharmaceutical care: past, present and future. Curr Pharm Des 2004; 10(31): 3931-46.
109. Marik PE. Propofol: therapeutic indications and side-effects. Curr Pharm Des 2004; 10(29): 3639-49.