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Vol. 12. Issue 6.
Pages 683-708 (November - December 2006)
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Vol. 12. Issue 6.
Pages 683-708 (November - December 2006)
Artigo de Revisão\Revision Article
Open Access
Os factores genéticos da asma
Asthma genetic factors
Visits
5230
Paula Alexandra Videira1, Luís Miguel Borrego2, Hélder Trindade3
1 Assistente Convidada Doutorada, Faculdade de Ciências Médicas, Departamento de Imunologia Universidade Nova de Lisboa
2 Assistente Convidado. Assistente Hospitalar de Imunoalergologia do Hospital Dona Estefânia, Faculdade de Ciências Médicas, Departamento de Imunologia Universidade Nova de Lisboa
3 Professor Associado Convidado com Agregação, Faculdade de Ciências Médicas, Departamento de Imunologia, Universidade Nova de Lisboa
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Resumo

A asma brônquica é uma doença inflamatória crónica das vias aéreas, de prevalência crescente, particularmente na infância, sendo considerado um importante problema de saúde pública.

É reconhecidamente uma doença de transmissão familiar, sendo um desafio a descrição e potencial identificação dos genes envolvidos na sua génese.

Pretende-se com o presente artigo de revisão explicitar exaustivamente os genes associados a esta patologia, bem como esclarecer os métodos laboratoriais que permitem a sua identificação.

Rev Port Pneumol 2006; XII (6): 683-708

Palavras-chave:
Asma
susceptibilidade genética
genome wide screen
estudos de associação
farmacogenética
Abstract

Asthma is a chronic inflammatory airways disease, with a rising prevalence, particularly in childhood, and is considered an important Public Health problem.

It’s familial transmission is recognised, while the description and identification of the genes implicated in this disease are a challenge.

In this revision paper the authors give a comprehensive explanation of the associated genes as well as the laboratorial methods that allow their identification.

Rev Port Pneumol 2006; XII (6): 683-708

Key-words:
Asthma
genetic susceptibility
genome wide screen
association studies
pharmacogenetics
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Bibliografia
[1.]
C. Nunes, S. Ladeira, J. Rosado Pinto.
Definição, epidemiologia e classificação da asma na criança.
A criança asmática no mundo da alergia, pp. 35-55
[2.]
National Institutes of Health NHLBI.
Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, National Institutes of Health Publication, (2002),
[3.]
S.T. Holgate.
The epidemic of allergy and asthma.
Nature, 402 (1999), pp. B2-B4
[4.]
G.H. Koppelman, H. Los, D.S. Postma.
Genetic and environment in asthma: the answer of twin studies.
Eur Respir J, 13 (1999), pp. 2-4
[5.]
J.A. Black, H.E. Lewis, C.K. Thacker, A.K. Thould.
Tristan da Cunha: General Medical Investigations.
Br Med J, 5364 (1963), pp. 1013-1024
[6.]
M.N. Blumenthal.
The role of genetics in the development of asthma and atopy.
Curr Opin Allergy Clin Immunol, 5 (2005), pp. 141-145
[7.]
D.L. Lind, S. Choudhry, N. Ung, E. Ziv, P.C. Avila, K. Salari, et al.
ADAM33 is not associated with asthma in Puerto Rican or Mexican populations.
Am J Respir Crit Care Med, 168 (2003), pp. 1312-1316
[8.]
N.E. Morton.
Logarithm of odds (lods) for linkage in complex inheritance.
Proc Natl Acad Sci U S A, 93 (1996), pp. 3471-3476
[9.]
S. Hoffjan, D. Nicolae, C. Ober.
Association studies for asthma and atopic diseases: a comprehensive review of the literature.
Respir Res, 4 (2003), pp. 14
[10.]
W.C. Lee.
Searching for disease-susceptibility loci by testing for Hardy-Weinberg disequilibrium in a gene bank of affected individuals.
Am J Epidemiol, 158 (2003), pp. 397-400
[11.]
E. Lander, L. Kruglyak.
Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results.
Nat Genet, 11 (1995), pp. 241-247
[12.]
W.O. Cookson.
Asthma genetics.
Chest, 121 (2002), pp. 7S-13S
[13.]
S. Hoffjan, C. Ober.
Present status on the genetic studies of asthma.
Curr Opin Immunol, 14 (2002), pp. 709-717
[14.]
T.D. Howard, D.A. Meyers, E.R. Bleecker.
Mapping susceptibility genes for allergic diseases.
Chest, 123 (2003), pp. 363S-368S
[15.]
M. Allen, A. Heinzmann, E. Noguchi, G. Abecasis, J. Broxholme, C.P. Ponting, S. Bhattacharyya, J. Tinsley, et al.
Positional cloning of a novel gene influencing asthma from chromosome 2q14.
Nat Genet, 35 (2003), pp. 258-263
[16.]
H. Gohlke, T. Illig, M. Bahnweg, N. Klopp, E. Andre, J. Altmuller, N. Herbon, M. Werner, et al.
Association of the interleukin-1 receptor antagonist gene with asthma.
Am J Respir Crit Care Med, 169 (2004), pp. 1217-1223
[17.]
M. Kabesch, D. Carr, S.K. Weiland, E. von Mutius.
Association between polymorphisms in serine protease inhibitor, kazal type 5 and asthma phenotypes in a large German population sample.
Clin Exp Allergy, 34 (2004), pp. 340-345
[18.]
H. Jongepier, G.H. Koppelman, I.M. Nolte, M. Bruinenberg, E.R. Bleecker, D.A. Meyers, G.J. te Meerman, D.S. Postma.
Polymorphisms in SPINK5 are not associated with asthma in a Dutch population.
J Allergy Clin Immunol, 115 (2005), pp. 486-492
[19.]
Y. Zhang, N.I. Leaves, G.G. Anderson, C.P. Ponting, J. Broxholme, R. Holt, P. Edser, S. Bhattacharyya, et al.
Positional cloning of a quantitative trait locus on chromosome 13q14 that influences immunoglobulin E levels and asthma.
Nat Genet, 34 (2003), pp. 181-186
[20.]
E. Melen, S. Bruce, G. Doekes, M. Kabesch, T. Laitinen, R. Lauener, C.M. Lindgren, J. Riedler, et al.
Haplotypes of G protein-coupled receptor 154 are associated with childhood allergy and asthma.
Am J Respir Crit Care Med, 171 (2005), pp. 1089-1095
[21.]
M.S. Kormann, D. Carr, N. Klopp, T. Illig, W. Leupold, C. Fritzsch, S.K. Weiland, E. von Mutius, et al.
G-Proteincoupled receptor polymorphisms are associated with asthma in a large German population.
Am J Respir Crit Care Med, 171 (2005), pp. 1358-1362
[22.]
T. Laitinen, A. Polvi, P. Rydman, J. Vendelin, V. Pulkkinen, P. Salmikangas, S. Makela, M. Rehn, et al.
Characterization of a common susceptibility locus for asthma-related traits.
Science, 304 (2004), pp. 300-304
[23.]
H.D. Shin, K.S. Park, C.S. Park.
Lack of association of GPRA (G protein-coupled receptor for asthma susceptibility) haplotypes with high serum IgE or asthma in a Korean population.
J Allergy Clin Immunol, 114 (2004), pp. 1226-1227
[24.]
C.D. Veal, N.J. Reynolds, S.J. Meggitt, M.H. Allen, C.M. Lindgren, J. Kere, R.C. Trembath, J.N. Barker.
Absence of association between asthma and high serum immunoglobulin E associated GPRA haplotypes and adult atopic dermatitis.
J Invest Dermatol, 125 (2005), pp. 399-401
[25.]
K. Shimoda, J. van Deursen, M.Y. Sangster, S.R. Sarawar, R.T. Carson, R.A. Tripp, C. Chu, F.W. Quelle, et al.
Lack of IL-4-induced Th2 response and IgE class switching in mice with disrupted Stat6 gene.
Nature, 380 (1996), pp. 630-633
[26.]
P.S. Gao, X.Q. Mao, M.H. Roberts, Y. Arinobu, M. Akaiwa, T. Enomoto, Y. Dake, M. Kawai, et al.
Variants of STAT6 (signal transducer and activator of transcription 6) in atopic asthma.
J Med Genet, 37 (2000), pp. 380-382
[27.]
K. Tamura, H. Arakawa, M. Suzuki, Y. Kobayashi, H. Mochizuki, M. Kato, K. Tokuyama, A. Morikawa.
Novel dinucleotide repeat polymorphism in the first exon of the STAT-6 gene is associated with allergic diseases.
Clin Exp Allergy, 31 (2001), pp. 1509-1514
[28.]
K. Tamura, M. Suzuki, H. Arakawa, K. Tokuyama, A. Morikawa.
Linkage and association studies of STAT6 gene polymorphisms and allergic diseases.
Int Arch Allergy Immunol, 131 (2003), pp. 33-38
[29.]
P.S. Gao, N.M. Heller, W. Walker, C.H. Chen, M. Moller, B. Plunkett, M.H. Roberts, R.P. Schleimer, et al.
Variation in dinucleotide (GT) repeat sequence in the first exon of the STAT6 gene is associated with atopic asthma and differentially regulates the promoter activity in vitro.
J Med Genet, 41 (2004), pp. 535-539
[30.]
M. Pykalainen, R. Kinos, S. Valkonen, P. Rydman, M. Kilpelainen, L.A. Laitinen, J. Karjalainen, M. Nieminen, et al.
Association analysis of common variants of STAT6, GATA3, and STAT4 to asthma and high serum IgE phenotypes.
J Allergy Clin Immunol, 115 (2005), pp. 80-87
[31.]
S. Weidinger, N. Klopp, S. Wagenpfeil, L. Rummler, M. Schedel, M. Kabesch, T. Schafer, U. Darsow, et al.
Association of a STAT 6 haplotype with elevated serum IgE levels in a population based cohort of white adults.
J Med Genet, 41 (2004), pp. 658-663
[32.]
M. Schedel, D. Carr, N. Klopp, B. Woitsch, T. Illig, D. Stachel, I. Schmid, C. Fritzsch, et al.
A signal transducer and activator of transcription 6 haplotype influences the regulation of serum IgE levels.
J Allergy Clin Immunol, 114 (2004), pp. 1100-1105
[33.]
P. Van Eerdewegh, R.D. Little, J. Dupuis, R.G. Del Mastro, K. Falls, J. Simon, D. Torrey, S. Pandit, et al.
Association of the ADAM33 gene with asthma and bronchial hyperresponsiveness.
Nature, 418 (2002), pp. 426-430
[34.]
J. Xu, D.A. Meyers, C. Ober, M.N. Blumenthal, B. Mellen, K.C. Barnes, R.A. King, L.A. Lester, et al.
Genomewide screen and identification of gene-gene interactions for asthma-susceptibility loci in three U.S. populations: collaborative study on the genetics of asthma.
Am J Hum Genet, 68 (2001), pp. 1437-1446
[35.]
J.H. Lee, H.S. Park, S.W. Park, A.S. Jang, S.T. Uh, T. Rhim, C.S. Park, S.J. Hong, et al.
ADAM33 polymorphism: association with bronchial hyper-responsiveness in Korean asthmatics.
Clin Exp Allergy, 34 (2004), pp. 860-865
[36.]
H. Jongepier, H.M. Boezen, A. Dijkstra, T.D. Howard, J.M. Vonk, G.H. Koppelman, S.L. Zheng, D.A. Meyers, et al.
Polymorphisms of the ADAM33 gene are associated with accelerated lung function decline in asthma.
Clin Exp Allergy, 34 (2004), pp. 757-760
[37.]
C.C. van Diemen, D.S. Postma, J.M. Vonk, M. Bruinenberg, J.P. Schouten, H.M. Boezen.
A disintegrin and metalloprotease 33 polymorphisms and lung function decline in the general population.
Am J Respir Crit Care Med, 172 (2005), pp. 329-333
[38.]
M. Werner, N. Herbon, H. Gohlke, J. Altmuller, M. Knapp, J. Heinrich, M. Wjst.
Asthma is associated with single-nucleotide polymorphisms in ADAM33.
Clin Exp Allergy, 34 (2004), pp. 26-31
[39.]
A. Simpson, N. Maniatis, F. Jury, J.A. Cakebread, L.A. Lowe, S.T. Holgate, A. Woodcock, W.E. Ollier, et al.
Polymorphisms in a disintegrin and metalloprotease 33 (ADAM33) predict impaired early-life lung function.
Am J Respir Crit Care Med, 172 (2005), pp. 55-60
[40.]
J. Blakey, E. Halapi, U.S. Bjornsdottir, A. Wheatley, S. Kristinsson, R. Upmanyu, K. Stefansson, H. Hakonarson, et al.
Contribution of ADAM33 polymorphisms to the population risk of asthma.
Thorax, 60 (2005), pp. 274-276
[41.]
S.T. Holgate, D.E. Davies, R.M. Powell, J.W. Holloway.
ADAM33: a newly identified protease involved in airway remodelling.
Pulm Pharmacol Ther, 19 (2006), pp. 3-11
[42.]
B.A. Raby, E.K. Silverman, D.J. Kwiatkowski, C. Lange, R. Lazarus, S.T. Weiss.
ADAM33 polymorphisms and phenotype associations in childhood asthma.
J Allergy Clin Immunol, 113 (2004), pp. 1071-1078
[43.]
T.D. Howard, D.S. Postma, H. Jongepier, W.C. Moore, G.H. Koppelman, S.L. Zheng, J. Xu, E.R. Bleecker, et al.
Association of a disintegrin and metalloprotease 33 (ADAM33) gene with asthma in ethnically diverse populations.
J Allergy Clin Immunol, 112 (2003), pp. 717-722
[44.]
S.D. Shapiro, C.A. Owen.
ADAM-33 surfaces as an asthma gene.
N Engl J Med, 347 (2002), pp. 936-938
[45.]
S.P. Umland, C.G. Garlisi, H. Shah, Y. Wan, J. Zou, K.E. Devito, W.M. Huang, E.L. Gustafson, R. Ralston.
Human ADAM33 messenger RNA expression profile and posttranscriptional regulation.
Am J Respir Cell Mol Biol, 29 (2003), pp. 571-582
[46.]
D. Nicolae, N.J. Cox, L.A. Lester, D. Schneider, Z. Tan, C. Billstrand, S. Kuldanek, J. Donfack, et al.
Fine mapping and positional candidate studies identify HLA-G as an asthma susceptibility gene on chromosome 6p21.
Am J Hum Genet, 76 (2005), pp. 349-357
[47.]
T.V. Hviid.
HLA-G in human reproduction: aspects of genetics, function and pregnancy complications.
Hum Reprod Update, 12 (2006), pp. 209-232
[48.]
R. Rizzo, C.E. Mapp, L. Melchiorri, P. Maestrelli, A. Visentin, S. Ferretti, I. Bononi, D. Miotto, et al.
Defective production of soluble HLA-G molecules by peripheral blood monocytes in patients with asthma.
J Allergy Clin Immunol, 115 (2005), pp. 508-513
[49.]
R. Temple, E. Allen, J. Fordham, S. Phipps, H.C. Schneider, K. Lindauer, I. Hayes, J. Lockey, et al.
Microarray analysis of eosinophils reveals a number of candidate survival and apoptosis genes.
Am J Respir Cell Mol Biol, 25 (2001), pp. 425-433
[50.]
C. Laprise, R. Sladek, A. Ponton, M.C. Bernier, T.J. Hudson, M. Laviolette.
Functional classes of bronchial mucosa genes that are differentially expressed in asthma.
BMC Genomics, 5 (2004), pp. 21
[51.]
N.N. Hansel, S.C. Hilmer, S.N. Georas, L.M. Cope, J. Guo, R.A. Irizarry, G.B. Diette.
Oligonucleotide-microarray analysis of peripheral-blood lymphocytes in severe asthma.
J Lab Clin Med, 145 (2005), pp. 263-274
[52.]
J.R. Guajardo, K.W. Schleifer, M.O. Daines, R.M. Ruddy, B.J. Aronow, M. Wills-Karp, G.K. Hershey.
Altered gene expression profiles in nasal respiratory epithelium reflect stable versus acute childhood asthma.
J Allergy Clin Immunol, 115 (2005), pp. 243-251
[53.]
C.M. Lilly, H. Tateno, T. Oguma, E. Israel, L.A. Sonna.
Effects of allergen challenge on airway epithelial cell gene expression.
Am J Respir Crit Care Med, 171 (2005), pp. 579-586
[54.]
N. Yuyama, D.E. Davies, M. Akaiwa, K. Matsui, Y. Hamasaki, Y. Suminami, N.L. Yoshida, M. Maeda, et al.
Analysis of novel disease-related genes in bronchial asthma.
Cytokine, 19 (2002), pp. 287-296
[55.]
N. Zimmermann, N.E. King, J. Laporte, M. Yang, A. Mishra, S.M. Pope, E.E. Muntel, D.P. Witte, et al.
Dissection of experimental asthma with DNA microarray analysis identifies arginase in asthma pathogenesis.
J Clin Invest, 111 (2003), pp. 1863-1874
[56.]
J. Zou, S. Young, F. Zhu, F. Gheyas, S. Skeans, Y. Wan, L. Wang, W. Ding, et al.
Microarray profile of differentially expressed genes in a monkey model of allergic asthma.
Genome Biol, 3 (2002),
[57.]
M. Benson, M. Olsson, M. Rudemo, G. Wennergren, L.O. Cardell.
Pros and cons of microarray technology in allergy research.
Clin Exp Allergy, 34 (2004), pp. 1001-1006
[58.]
C. D’Ambrosio, L. Gatta, S. Bonini.
The future of microarray technology: networking the genome search.
[59.]
D.A. Kuperman, C.C. Lewis, P.G. Woodruff, M.W. Rodriguez, Y.H. Yang, G.M. Dolganov, J.V. Fahy, D.J. Erle.
Dissecting asthma using focused transgenic modeling and functional genomics.
J Allergy Clin Immunol, 116 (2005), pp. 305-311
[60.]
A.J. Sandford, T. Chagani, S. Zhu, T.D. Weir, T.R. Bai, J.J. Spinelli, J.M. Fitzgerald, N.A. Behbehani, et al.
Polymorphisms in the IL4, IL4RA, and FCERIB genes and asthma severity.
J Allergy Clin Immunol, 106 (2000), pp. 135-140
[61.]
E. Noguchi, Y. Nukaga-Nishio, Z. Jian, Y. Yokouchi, M. Kamioka, K. Yamakawa-Kobayashi, H. Hamaguchi, A. Matsui, et al.
Haplotypes of the 5' region of the IL-4 gene and SNPs in the intergene sequence between the IL-4 and IL-13 genes are associated with atopic asthma.
Hum Immunol, 62 (2001), pp. 1251-1257
[62.]
T.D. Howard, G.H. Koppelman, J. Xu, S.L. Zheng, D.S. Postma, D.A. Meyers, E.R. Bleecker.
Gene-gene interaction in asthma: IL4RA and IL13 in a Dutch population with asthma.
Am J Hum Genet, 70 (2002), pp. 230-236
[63.]
C. Ober, S.A. Leavitt, A. Tsalenko, T.D. Howard, D.M. Hoki, R. Daniel, D.L. Newman, X. Wu, et al.
Variation in the interleukin 4-receptor alpha gene confers susceptibility to asthma and atopy in ethnically diverse populations.
Am J Hum Genet, 66 (2000), pp. 517-526
[64.]
S. Zhu, M. Chan-Yeung, A.B. Becker, H. Dimich-Ward, A.C. Ferguson, J. Manfreda, W.T. Watson, P.D. Pare, et al.
Polymorphisms of the IL-4, TNF-alpha, and Fcepsilon RIbeta genes and the risk of allergic disorders in at-risk infants.
Am J Respir Crit Care Med, 161 (2000), pp. 1655-1659
[65.]
I. Suzuki, N. Hizawa, E. Yamaguchi, Y. Kawakami.
Association between a C+33T polymorphism in the IL-4 promoter region and total serum IgE levels.
Clin Exp Allergy, 30 (2000), pp. 1746-1749
[66.]
T.D. Howard, P.A. Whittaker, A.L. Zaiman, G.H. Koppelman, J. Xu, M.T. Hanley, D.A. Meyers, D.S. Postma, et al.
Identification and association of polymorphisms in the interleukin-13 gene with asthma and atopy in a Dutch population.
Am J Respir Cell Mol Biol, 25 (2001), pp. 377-384
[67.]
A. Heinzmann, X.Q. Mao, M. Akaiwa, R.T. Kreomer, P.S. Gao, K. Ohshima, R. Umeshita, Y. Abe, et al.
Genetic variants of IL-13 signalling and human asthma and atopy.
Hum Mol Genet, 9 (2000), pp. 549-559
[68.]
P.E. Graves, M. Kabesch, M. Halonen, C.J. Holberg, M. Baldini, C. Fritzsch, S.K. Weiland, R.P. Erickson, et al.
A cluster of seven tightly linked polymorphisms in the IL-13 gene is associated with total serum IgE levels in three populations of white children.
J Allergy Clin Immunol, 105 (2000), pp. 506-513
[69.]
M.J. Basehore, T.D. Howard, L.A. Lange, W.C. Moore, G.A. Hawkins, P.L. Marshik, M.S. Harkins, D.A. Meyers, et al.
A comprehensive evaluation of IL4 variants in ethnically diverse populations: association of total serum IgE levels and asthma in white subjects.
J Allergy Clin Immunol, 114 (2004), pp. 80-87
[70.]
D.A. Meyers, D.S. Postma, O.C. Stine, G.H. Koppelman, E.J. Ampleford, H. Jongepier, T.D. Howard, E.R. Bleecker.
Genome screen for asthma and bronchial hyperresponsiveness: interactions with passive smoke exposure.
J Allergy Clin Immunol, 115 (2005), pp. 1169-1175
[71.]
A genome-wide search for asthma susceptibility loci in ethnically diverse populations. The Collaborative Study on the Genetics of Asthma (CSGA).
Nat Genet, 15 (1997), pp. 389-392
[72.]
C. Ober, N.J. Cox, M. Abney, A. Di Rienzo, E.S. Lander, B. Changyaleket, H. Gidley, B. Kurtz, et al.
Genome-wide search for asthma susceptibility loci in a founder population. The Collaborative Study on the Genetics of Asthma.
Hum Mol Genet, 7 (1998), pp. 1393-1398
[73.]
M. Wills-Karp.
Interleukin-13 in asthma pathogenesis.
Immunol Rev, 202 (2004), pp. 175-190
[74.]
A.E. Kelly-Welch, E.M. Hanson, M.R. Boothby, A.D. Keegan.
Interleukin-4 and interleukin-13 signaling connections maps.
Science, 300 (2003), pp. 1527-1528
[75.]
T.C. van der Pouw Kraan, A. van Veen, L.C. Boeije, S.A. van Tuyl, E.R. de Groot, S.O. Stapel, A. Bakker, C.L. Verweij, et al.
An IL-13 promoter polymorphism associated with increased risk of allergic asthma.
Genes Immun, 1 (1999), pp. 61-65
[76.]
K. Arima, K. Sato, G. Tanaka, S. Kanaji, T. Terada, E. Honjo, R. Kuroki, Y. Matsuo, et al.
Characterization of the interaction between interleukin-13 and interleukin-13 receptors.
J Biol Chem, 280 (2005), pp. 24915-24922
[77.]
K. Arima, R. Umeshita-Suyama, Y. Sakata, M. Akaiwa, X.Q. Mao, T. Enomoto, Y. Dake, S. Shimazu, et al.
Upregulation of IL-13 concentration in vivo by the IL13 variant associated with bronchial asthma.
J Allergy Clin Immunol, 109 (2002), pp. 980-987
[78.]
A.J. Walley, W.O. Cookson.
Investigation of an interleukin-4 promoter polymorphism for associations with asthma and atopy.
J Med Genet, 33 (1996), pp. 689-692
[79.]
R. Nagarkatti, R. Kumar, S.K. Sharma, B. Ghosh.
Association of IL4 gene polymorphisms with asthma in North Indians.
Int Arch Allergy Immunol, 134 (2004), pp. 206-212
[80.]
I. Shirakawa, K.A. Deichmann, I. Izuhara, I. Mao, C.N. Adra, J.M. Hopkin.
Atopy and asthma: genetic variants of IL-4 and IL-13 signalling.
Immunol Today, 21 (2000), pp. 60-64
[81.]
D.S. Faffe, T. Whitehead, P.E. Moore, S. Baraldo, L. Flynt, K. Bourgeois, R.A. Panettieri, S.A. Shore.
IL-13 and IL-4 promote TARC release in human airway smooth muscle cells: role of IL-4 receptor genotype.
Am J Physiol Lung Cell Mol Physiol, 285 (2003), pp. L907-L914
[82.]
H. Mitsuyasu, Y. Yanagihara, X.Q. Mao, P.S. Gao, Y. Arinobu, K. Ihara, A. Takabayashi, T. Hara, et al.
Cutting edge: dominant effect of Ile50Val variant of the human IL-4 receptor alpha-chain in IgE synthesis.
J Immunol, 162 (1999), pp. 1227-1231
[83.]
E. Noguchi, M. Shibasaki, T. Arinami, K. Takeda, Y. Yokouchi, K. Kobayashi, N. Imoto, S. Nakahara, et al.
No association between atopy/asthma and the ILe50Val polymorphism of IL-4 receptor.
Am J Respir Crit Care Med, 160 (1999), pp. 342-345
[84.]
X. Liu, T.H. Beaty, P. Deindl, S.K. Huang, S. Lau, C. Sommerfeld, M.D. Fallin, W.H. Kao, et al.
Associations between total serum IgE levels and the 6 potentially functional variants within the genes IL4, IL13, and IL4RA in German children: the German Multicenter Atopy Study.
J Allergy Clin Immunol, 112 (2003), pp. 382-388
[85.]
L.J. Palmer, P.J. Rye, N.A. Gibson, M.F. Moffatt, J. Goldblatt, P.R. Burton, W.O. Cookson, P.N. Lesouef.
Association of FcepsilonR1-beta polymorphisms with asthma and associated traits in Australian asthmatic families.
Clin Exp Allergy, 29 (1999), pp. 1555-1562
[86.]
X. Zhang, W. Zhang, D. Qiu, A. Sandford, W.C. Tan.
The E237G polymorphism of the high-affinity IgE receptor beta chain and asthma.
Ann Allergy Asthma Immunol, 93 (2004), pp. 499-503
[87.]
B. Korzycka-Zaborowska, J.M. Hopkin, P. Gorski.
Genetic variants of FcepsilonRIbeta and Il-4 and atopy in a Polish population.
Allergol Immunopathol (Madr), 32 (2004), pp. 53-58
[88.]
Y.L. Lee, T.R. Hsiue, Y.C. Lee, Y.C. Lin, Y.L. Guo.
The association between glutathione S-transferase P1, M1 polymorphisms and asthma in Taiwanese schoolchildren.
Chest, 128 (2005), pp. 1156-1162
[89.]
Y.L. Lee, Y.C. Lin, Y.C. Lee, J.Y. Wang, T.R. Hsiue, Y.L. Guo.
Glutathione S-transferase P1 gene polymorphism and air pollution as interactive risk factors for childhood asthma.
Clin Exp Allergy, 34 (2004), pp. 1707-1713
[90.]
A.S. Aynacioglu, M. Nacak, A. Filiz, E. Ekinci, I. Roots.
Protective role of glutathione S-transferase P1 (GSTP1) Val105Val genotype in patients with bronchial asthma.
Br J Clin Pharmacol, 57 (2004), pp. 213-217
[91.]
M.R. Hill, A.L. James, J.A. Faux, G. Ryan, J.M. Hopkin, P. le Souef, A.W. Musk, W.O. Cookson.
Fc epsilon RI-beta polymorphism and risk of atopy in a general population sample.
BMJ, 311 (1995), pp. 776-779
[92.]
F. Child, W. Lenney, S. Clayton, S. Davies, P.W. Jones, J.E. Alldersea, R.C. Strange, A.A. Fryer.
The association of maternal but not paternal genetic variation in GSTP1 with asthma phenotypes in children.
Respir Med, 97 (2003), pp. 1247-1256
[93.]
C. Brasch-Andersen, L. Christiansen, Q. Tan, A. Haagerup, J. Vestbo, T.A. Kruse.
Possible gene dosage effect of glutathione-S-transferases on atopic asthma: using real-time PCR for quantification of GSTM1 and GSTT1 gene copy numbers.
Hum Mutat, 24 (2004), pp. 208-214
[94.]
M.F. Moffatt, A. James, G. Ryan, A.W. Musk, W.O. Cookson.
Extended tumour necrosis factor/HLA-DR haplotypes and asthma in an Australian population sample.
Thorax, 54 (1999), pp. 757-761
[95.]
A.G. Randolph, C. Lange, E.K. Silverman, R. Lazarus, S.T. Weiss.
Extended haplotype in the tumor necrosis factor gene cluster is associated with asthma and asthmarelated phenotypes.
Am J Respir Crit Care Med, 172 (2005), pp. 687-692
[96.]
H.S. Chang, J.S. Kim, J.H. Lee, J.I. Cho, T.Y. Rhim, S.T. Uh, B.L. Park, I.Y. Chung, et al.
A single nucleotide polymorphism on the promoter of eotaxin1 associates with its mRNA expression and asthma phenotypes.
J Immunol, 174 (2005), pp. 1525-1531
[97.]
K. Fukunaga, K. Asano, X.Q. Mao, P.S. Gao, M.H. Roberts, T. Oguma, T. Shiomi, M. Kanazawa, et al.
Genetic polymorphisms of CC chemokine receptor 3 in Japanese and British asthmatics.
Eur Respir J, 17 (2001), pp. 59-63
[98.]
K.G. Tantisira, S.T. Weiss.
The pharmacogenetics of asthma: an update.
Curr Opin Mol Ther, 7 (2005), pp. 209-217
[99.]
L.J. Kay, P.T. Peachell.
Mast cell beta2-adrenoceptors.
Chem Immunol Allergy, 87 (2005), pp. 145-153
[100.]
L.J. Palmer, E.S. Silverman, S.T. Weiss, J.M. Drazen.
Pharmacogenetics of asthma.
Am J Respir Crit Care Med, 165 (2002), pp. 861-866
[101.]
S.B. Liggett.
The pharmacogenetics of beta2-adrenergic receptors: relevance to asthma.
J Allergy Clin Immunol, 105 (2000), pp. S487-S492
[102.]
J. Turki, J. Pak, S.A. Green, R.J. Martin, S.B. Liggett.
Genetic polymorphisms of the beta 2-adrenergic receptor in nocturnal and nonnocturnal asthma. Evidence that Gly16 correlates with the nocturnal phenotype.
J Clin Invest, 95 (1995), pp. 1635-1641
[103.]
S.A. Green, J. Turki, M. Innis, S.B. Liggett.
Aminoterminal polymorphisms of the human beta 2-adrenergic receptor impart distinct agonist-promoted regulatory properties.
Biochemistry, 33 (1994), pp. 9414-9419
[104.]
K.C. Barnes.
Atopy and asthma genes – where do we stand?.
Allergy, 55 (2000), pp. 803-817
[105.]
S.B. Liggett.
Pharmacogenetics of beta-1- and beta2-adrenergic receptors.
Pharmacology, 61 (2000), pp. 167-173
[106.]
C.M. Drysdale, D.W. McGraw, C.B. Stack, J.C. Stephens, R.S. Judson, K. Nandabalan, K. Arnold, G. Ruano, et al.
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 (2000), pp. 10483-10488
[107.]
D.Y. Leung, R.J. Martin, S.J. Szefler, E.R. Sher, S. Ying, A.B. Kay, Q. Hamid.
Dysregulation of interleukin 4, interleukin 5, and interferon gamma gene expression in steroid-resistant asthma.
J Exp Med, 181 (1995), pp. 33-40
[108.]
D.Y. Leung, Q. Hamid, A. Vottero, S.J. Szefler, W. Surs, E. Minshall, G.P. Chrousos, D.J. Klemm.
Association of glucocorticoid insensitivity with increased expression of glucocorticoid receptor beta.
J Exp Med, 186 (1997), pp. 1567-1574
[109.]
K.G. Tantisira, S. Lake, E.S. Silverman, L.J. Palmer, R. Lazarus, E.K. Silverman, S.B. Liggett, E.W. Gelfand, et al.
Corticosteroid pharmacogenetics: association of sequence variants in CRHR1 with improved lung function in asthmatics treated with inhaled corticosteroids.
Hum Mol Genet, 13 (2004), pp. 1353-1359
[110.]
J.M. Drazen, C.N. Yandava, L. Dube, N. Szczerback, R. Hippensteel, A. Pillari, E. Israel, N. Schork, et al.
Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment.
Nat Genet, 22 (1999), pp. 168-170
[111.]
K. Yoshikawa, E. Matsui, H. Kaneko, T. Fukao, R. Inoue, T. Teramoto, S. Shinoda, O. Fukutomi, et al.
A novel single-nucleotide substitution, Glu 4 Lys, in the leukotriene C4 synthase gene associated with allergic diseases.
Int J Mol Med, 16 (2005), pp. 827-831
[112.]
R. Ramires, M.F. Caiaffa, A. Tursi, J.Z. Haeggstrom, L. Macchia.
Novel inhibitory effect on 5-lipoxygenase activity by the anti-asthma drug montelukast.
Biochem Biophys Res Commun, 324 (2004), pp. 815-821
[113.]
Y. Sasaki, K. Ihara, S. Ahmed, K. Yamawaki, K. Kusuhara, H. Nakayama, S. Nishima, T. Hara.
Lack of association between atopic asthma and polymorphisms of the histamine H1 receptor, histamine H2 receptor, and histamine N-methyltransferase genes.
Immunogenetics, 51 (2000), pp. 238-240
[114.]
L. Yan, R.E. Galinsky, J.A. Bernstein, S.B. Liggett, R.M. Weinshilboum.
Histamine N-methyltransferase pharmacogenetics: association of a common functional polymorphism with asthma.
Pharmacogenetics, 10 (2000), pp. 261-266
[115.]
S. Sharma, D. Mann, T.P. Singh, B. Ghosh.
Lack of association of histamine-N-methyltransferase (HNMT) polymorphisms with asthma in the Indian population.
J Hum Genet, 50 (2005), pp. 611-617
[116.]
P. Deindl, S. Peri-Jerkan, K. Deichmann, B. Niggemann, S. Lau, C. Sommerfeld, C. Sengler, S. Muller, et al.
No association of histamine- N-methyltransferase polymorphism with asthma or bronchial hyperresponsiveness in two German pediatric populations.
Pediatr Allergy Immunol, 16 (2005), pp. 40-42
[117.]
E. Israel, V.M. Chinchilli, J.G. Ford, H.A. Boushey, R. Cherniack, T.J. Craig, A. Deykin, J.K. Fagan, et al.
Use of regularly scheduled albuterol treatment in asthma: genotype-stratified, randomised, placebo-controlled cross-over trial.
Lancet, 364 (2004), pp. 1505-1512
[118.]
S.E. Daniels, S. Bhattacharrya, A. James, N.I. Leaves, A. Young, M.R. Hill, J.A. Faux, G.F. Ryan, et al.
A genomewide search for quantitative trait loci underlying asthma.
Nature, 383 (1996), pp. 247-250
[119.]
N. Hizawa, L.R. Freidhoff, Y.F. Chiu, E. Ehrlich, C.A. Luehr, J.L. Anderson, D.L. Duffy, G.M. Dunston, et al.
Genetic regulation of Dermatophagoides pteronyssinus-specific IgE responsiveness: a genome-wide multipoint linkage analysis in families recruited through 2 asthmatic sibs. Collaborative Study on the Genetics of Asthma (CSGA).
J Allergy Clin Immunol, 102 (1998), pp. 436-442
[120.]
M. Wjst, G. Fischer, T. Immervoll, M. Jung, K. Saar, F. Rueschendorf, A. Reis, M. Ulbrecht, et al.
A genomewide search for linkage to asthma.
German Asthma Genetics Group. Genomics, 58 (1999), pp. 1-8
[121.]
M.H. Dizier, C. Besse-Schmittler, M. Guilloud-Bataille, I. Annesi-Maesano, M. Boussaha, J. Bousquet, D. Charpin, A. Degioanni, et al.
Genome screen for asthma and related phenotypes in the French EGEA study.
Am J Respir Crit Care Med, 162 (2000), pp. 1812-1818
[122.]
Y. Yokouchi, Y. Nukaga, M. Shibasaki, E. Noguchi, K. Kimura, S. Ito, M. Nishihara, K. Yamakawa-Kobayashi, et al.
Significant evidence for linkage of mite-sensitive childhood asthma to chromosome 5q31-q33 near the interleukin 12 B locus by a genome-wide search in Japanese families.
Genomics, 66 (2000), pp. 152-160
[123.]
C. Ober, A. Tsalenko, R. Parry, N.J. Cox.
A secondgeneration genomewide screen for asthma-susceptibility alleles in a founder population.
Am J Hum Genet, 67 (2000), pp. 1154-1162
[124.]
X. Xu, Z. Fang, B. Wang, C. Chen, W. Guang, Y. Jin, J. Yang, S. Lewitzky, et al.
A genomewide search for quantitative-trait loci underlying asthma.
Am J Hum Genet, 69 (2001), pp. 1271-1277
[125.]
T. Laitinen, M.J. Daly, J.D. Rioux, P. Kauppi, C. Laprise, T. Petays, T. Green, M. Cargill, et al.
A susceptibility locus for asthma-related traits on chromosome 7 revealed by genome-wide scan in a founder population.
Nat Genet, 28 (2001), pp. 87-91
[126.]
H. Hakonarson, U.S. Bjornsdottir, E. Halapi, S. Palsson, E. Adalsteinsdottir, D. Gislason, G. Finnbogason, T. Gislason, et al.
A major susceptibility gene for asthma maps to chromosome 14q24.
Am J Hum Genet, 71 (2002), pp. 483-491
[127.]
A. Haagerup, T. Bjerke, P.O. Schiotz, H.G. Binderup, R. Dahl, T.A. Kruse.
Asthma and atopy – a total genome scan for susceptibility genes.
Allergy, 57 (2002), pp. 680-686
[128.]
Postma DS, Meyers DA, Jongepier H, Howard TD, Koppelman GH, Bleecker ER. Genomewide screen for pulmonary function in 200 families ascertained for asthma. Am J Respir Crit Care Med 200; 172:446-452.
[129.]
J.Y. Wang, C.G. Lin, M.S. Bey, L. Wang, F.Y. Lin, L. Huang, L.S. Wu.
Discovery of genetic difference between asthmatic children with high IgE level and normal IgE level by whole genome linkage disequilibrium mapping using 763 autosomal STR markers.
J Hum Genet, 50 (2005), pp. 249-258
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