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The alliance of genes and environment in asthma and allergy

Nature volume 402, pages 5–11 (1999)Cite this article

Abstract

The diseases of asthma, eczema and hay fever are typified by reactions to common allergens, which are mediated by immunoglobulin E. These allergic diseases are increasing in prevalence, and are now a major source of disability throughout the developed world. They are the result of complex interactions between largely unknown genetic and environmental mechanisms.The identification of the environmental factors offers the real possibility of prevention of disease, and unravelling the genetics of allergic illnesses is likely to change their classification and treatment. Early life seems particularly important, when the initiation of allergic disease may result from genetic and environmental modification of the immune interaction between mother and child.

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Figure 1: Consequences of allergic inflammation.
Figure 2: The crystal structure of the birch pollen allergen, Bet v I.
Figure 3: Gene clusters affecting allergic inflammation.

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Notes

  1. *Terms in italic are defined in the glossary on p. 39.

References

  1. von Pirquet, C. Allergie. Münch. med. Wochenschr. 30, 1457 (1906).

    Google Scholar 

  2. Coca, A. F. & Cooke, R. A. On the phenomenon of hypersensitiveness. J. Immunol. 8, 163–182 (1923).

    CAS  Google Scholar 

  3. Smith, D. H. et al. A national estimate of the economic costs of asthma. Am. J. Respir. Crit. Care Med. 156, 787– 793 (1997).

    Article  CAS  PubMed  Google Scholar 

  4. Nowak, D., Volmer, T. & Wettengel, R. Asthma bronchiale—eine Krankheitskostenanalyse. Pneumologie 50, 364–371 (1996).

    CAS  PubMed  Google Scholar 

  5. National Asthma Campaign. Asthma Agenda (National Asthma Campaign, London, 1998).

  6. Stuart, M. Start-up 12–20 (April 1999).

  7. Sampson, H. A. Pathogenesis of eczema. Clin. Exp. Allergy 20, 459–467 (1990).

    Article  CAS  PubMed  Google Scholar 

  8. Schultz-Larsen, F. A genetic-epidemiologic study in a population-based twin sample. J. Am. Acad. Dermatol. 28, 719–723 (1993).

    Article  CAS  PubMed  Google Scholar 

  9. Cox, H. E. et al. Association of atopic dermatitis to the beta subunit of the high affinity Immunoglobulin E receptor. Br. J. Dermatol. 138, 182–187 (1998).

    Article  CAS  PubMed  Google Scholar 

  10. Moffatt, M. F. & Cookson, W. O. C. M. in Genetics of Asthma and Atopy (ed. Hall, I. P. ) (Monogr. Allergy 33, 71–97) (Karger, Basel, 1996).

    Google Scholar 

  11. Larsen, J. N., Sparholt, S. H. & Ipsen, H. Epitope structure of recombinant isoallergens of Bet v 1. J. Adv. Exp. Med. Biol. 409, 243– 249 (1996).

    Article  CAS  Google Scholar 

  12. Mueller, G. A., Benjamin, D. C., Rule, G. S. & Beirne, B. Tertiary structure of the major house dust mite allergen Der p 2: sequential and structural homologies. Biochemistry 37, 12707–12714 (1998).

    Article  CAS  PubMed  Google Scholar 

  13. Sigurs, N. et al.Appearance of atopic disease in relation to serum IgE antibodies in children followed up from birth for 4 to 15 years. J. Allergy Clin. Immunol. 94, 757–763 (1994).

    Article  CAS  PubMed  Google Scholar 

  14. Rona, R. J., Chinn, S. & Burney, P. G. Trends in the prevalence of asthma in Scottish and English primary school children 1982–92. Thorax 50, 992–993 (1995).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Aberg, N., Hesselmar, B., Aberg, B. & Eriksson, B. Increase of asthma, allergic rhinitis and eczema in Swedish schoolchildren between 1979 and 1991. Clin. Exp. Allergy 25, 815– 819 (1995).

    Article  CAS  PubMed  Google Scholar 

  16. Dubois, P., Degrave, E. & Vandenplas, O. Asthma and airway hyperresponsiveness among Belgian conscripts, 1978–91. Thorax 53, 101 –105 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. von Mutius, E., Fritzsch, C., Weiland, S. K., Roll, G. & Magnussen, H. Prevalence of asthma and allergic disorders among children in united Germany: a descriptive comparison. Brit. Med. J. 305, 1395–1399 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. von Mutius, E. et al.Prevalence of asthma and atopy in two areas of West and East Germany. Am. J. Respir. Crit. Care Med. 149, 358–364 (1994).

    Article  CAS  PubMed  Google Scholar 

  19. Bjorksten, B. et al. Prevalence of childhood asthma, rhinitis and eczema in Scandinavia and Eastern Europe. Eur. Respir. J. 12, 432–437 (1998).

    Article  CAS  PubMed  Google Scholar 

  20. von Mutius, E., Weiland, S. K., Fritzsch, C., Duhme, H. & Keil, U. Increasing prevalence of hay fever and atopy among children in Leipzig, East Germany. Lancet 351, 862–866 (1998).

    Article  CAS  PubMed  Google Scholar 

  21. The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee. Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema. Lancet 351, 1225– 1232 (1998).

    Article  Google Scholar 

  22. European Community Respiratory Health Survey (ECRHS). Variations in the prevalence of respiratory symptoms, self-reported asthma attacks, and use of asthma medication in the European Community Respiratory Health Survey (ECRHS). Eur. Respir. J. 9, 687–695 (1996).

    Article  Google Scholar 

  23. Von Ehrenstein, O., von Mutius, E., Illi, S., Hachmeister, A. & von Kries, R. Reduced prevalence of atopic diseases in children living on a farm. Epidemiology 9, S118 (1998).

    Google Scholar 

  24. Godfrey, R. C. Asthma and IgE levels in rural and urban communities of The Gambia. Clin. Allergy 5, 201–207 (1975).

    Article  CAS  PubMed  Google Scholar 

  25. Braun-Fahrländer, C. et al. Prevalence of hay fever and allergic sensitization in farmer's children and their peers living in the same rural community. Clin. Exp. Allergy 29, 28–34 ( 1999).

    Article  PubMed  Google Scholar 

  26. Staines, C. Childhood factors and adult atopy: results from the European Community Respiratory Health Survey. Am. J. Respir. Crit. Care Med. 157, A11 (1998).

    Google Scholar 

  27. von Mutius, E. et al. Skin test reactivity and number of siblings. Br. Med. J. 308, 692–695 ( 1994).

    Article  CAS  Google Scholar 

  28. Holt, P. G., McMenamin, C. & Nelson, D. Primary sensitisation to inhalant allergens during infancy. Pediatr. Allergy Immunol. 1, 3– 15 (1990).

    Article  Google Scholar 

  29. Sporik, R., Holgate, S., Platts-Mills, T. A. E. & Cogswells, J. J. Exposure to house dust mite allergen Der p I and the development of asthma in children. N. Engl. J. Med. 323, 502–507 (1990).

    Article  CAS  PubMed  Google Scholar 

  30. Bjorksten, B. Allergy priming early in life. Lancet 353, 167–168 (1999).

    Article  CAS  PubMed  Google Scholar 

  31. Rook, G. A. & Stanford, J. L. Give us this day our daily germs. Immunol. Today 19, 113– 116 (1998).

    Article  CAS  PubMed  Google Scholar 

  32. Anto, J. M. & Sunyer, J. A point-source asthma outbreak. Lancet 1, 900–903 ( 1986).

    Article  CAS  PubMed  Google Scholar 

  33. Duffy, D. L., Martin, N. G., Battistutta, D., Hopper, J. L. & Mathews, J. D. Genetics of asthma and hay fever in Australian twins. Am. Rev. Respir. Dis. 142, 1351–1358 (1990).

    Article  CAS  PubMed  Google Scholar 

  34. Lawrence, S. et al. Genetic analysis of atopy and asthma as quantitative traits and ordered polychotomies. Ann. Hum. Genet. 58, 359–368 (1994).

    Article  CAS  PubMed  Google Scholar 

  35. Holberg, C. et al. Segregation analysis of physician-diagnosed asthma in hispanic and non-hispanic white families. Am. J. Respir. Crit. Care Med. 154, 144–150 ( 1996).

    Article  CAS  PubMed  Google Scholar 

  36. Jenkins, M., Hopper, J. & Giles, G. Regressive logistic modelling of familial aggregation for asthma in 7,394 population-based nuclear families. Genet. Epidemiol. 14, 317–332 ( 1997).

    Article  CAS  PubMed  Google Scholar 

  37. Schultz Larsen, F., Holm, N. V. & Henningsen, K. Atopic dermatitis. A genetic epidemiologic study in a population-based twin sample. J. Am. Acad. Derm. 15, 487–494 (1986).

    Article  Google Scholar 

  38. Dold, S. et al. Genetic risk for asthma, allergic rhinitis and atopic dermatitis. Arch. Dis. Child. 67, 1018– 1022 (1992).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Blumenthal, M. N., Namborrdiri, K., Mendell, N., Gleich, C. & Elston, R. C. Genetic transmission of serum IgE levels. Am. J. Med. Genet. 10, 219– 228 (1981).

    Article  CAS  PubMed  Google Scholar 

  40. Borecki, I., Rao, D. C., Lalouel, J. M., McGue, L. & Gerrard, J. W. Demonstration of a common major gene with pleiotrophic effects on Immunoglobulin E and allergy. Genet. Epidemiol. 2, 327–338 ( 1985).

    Article  CAS  PubMed  Google Scholar 

  41. Collins, F. S. Positional cloning moves from perditional to traditional. Nature Genet. 9, 347–350 ( 1995).

    Article  CAS  PubMed  Google Scholar 

  42. Cookson, W. O. C. M., Sharp, P. A., Faux, J. A. & Hopkin, J. M. Linkage between Immunoglobulin E responses underlying asthma and rhinitis and chromosome 11q. Lancet 8650, 1292– 1295 (1989).

    Article  Google Scholar 

  43. Watson, M. et al. Exclusion from proximal 11q of a common gene with megaphenic effect on atopy. Ann. Hum. Genet. 59, 403 –411 (1995).

    Article  CAS  PubMed  Google Scholar 

  44. Hill, M. R. & Cookson, W. O. C. M. A new variant of the β subunit of the high-affinity receptor for Immunoglobulin E (FcεRI-β E237G): associations with measures of atopy and bronchial hyper-responsiveness. Hum. Mol. Genet. 5, 959– 962 (1996).

    Article  CAS  PubMed  Google Scholar 

  45. Shirakawa, T. et al. Association between atopic asthma and a coding variant of Fc epsilon RI beta in a Japanese population. Hum. Mol. Genet. 5, 1129–1130 (1996).

    Article  CAS  PubMed  Google Scholar 

  46. van Herwerden, L. et al. Linkage of high-affinity IgE receptor gene with bronchial hyperreactivity, even in absence of atopy. Lancet 346, 1262 –1265 (1995).

    Article  Google Scholar 

  47. Palmer, L. J. et al. FcεRI-β polymorphism and total serum IgE levels in endemically parasitised Australian Aboriginies. Am. J. Hum. Genet. 61, 182–188 ( 1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Shirakawa, T. S. et al. Association between atopy and variants of the β subunit of the high-affinity immunoglobulin E receptor. Nature Genet. 7, 125–129 (1994).

    Article  CAS  PubMed  Google Scholar 

  49. Rosenwasser, L. J. Genetics of atopy and asthma: promoter-based candidate gene studies for IL-4. Int. Arch. Allergy Immunol. 113, 61– 64 (1997).

    Article  CAS  PubMed  Google Scholar 

  50. Baldini, M. et al. A polymorphism in the 5′ flanking region of the CD14 gene is associated with circulating soluble CD14 levels and with total serum immunoglobulin E. Am. J. Respir. Cell Mol. Biol. 20 , 976–983 (1999).

    Article  CAS  PubMed  Google Scholar 

  51. Hershey, G. K., Friedrich, M. F., Esswein, L. A., Thomas, M. L. & Chatila, T. A. The association of atopy with a gain-of-function mutation in the alpha subunit of the interleukin-4 receptor. N. Engl. J. Med. 337, 1720– 1725 (1997).

    Article  CAS  PubMed  Google Scholar 

  52. Green, S. A., Turki, J., Innis, M. & Liggett, S. Amino-terminal polymorphisms of the human β2-adrenergic receptor impart distinct agonist-promoted regulatory properties. Biochemistry 33, 9414–9419 (1994).

    Article  CAS  PubMed  Google Scholar 

  53. Hall, I. P. Beta 2 adrenoceptor polymorphisms: are they clinically important? Thorax 51, 351–353 ( 1996).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Moffatt, M. F. & Cookson, W. O. C. M. Tumour necrosis factor haplotypes and asthma. Hum. Molec. Genet. 6, 551–554 (1997).

    Article  CAS  PubMed  Google Scholar 

  55. Shirakawa, T. et al. Linkage between severe atopy and chromosome 11q in Japanese families. Clin. Genet. 46, 125– 129 (1994).

    Google Scholar 

  56. Yandava, C. N. et al. Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment. Nature Genet. 22, 168–170 (1999).

    Article  PubMed  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  58. Gyapay, G. et al. The 1993-94 Genethon human genetic linkage map. Nature Genet. 7, 246–339 (1994).

    Article  CAS  PubMed  Google Scholar 

  59. Lander, E. & Kruglyak, L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nature Genet. 11, 241–247 ( 1995).

    Article  CAS  PubMed  Google Scholar 

  60. Cookson, W. O. & Palmer, L. J. Investigating the asthma phenotype. Clin. Exp. Allergy 28 (Suppl. 1), 88–89 (discussion 108–110) (1998).

    Article  PubMed  Google Scholar 

  61. Risch, N. & Zhang, H. Extreme discordant sib pairs for mapping quantitative trait loci in humans. Science 268, 1584–1589 (1995).

    Article  ADS  CAS  PubMed  Google Scholar 

  62. Marsh, D. G. et al. Linkage analysis of IL-4 and other chromosome 5q31. 1 markers and total serum IgE concentrations. Science 264, 1152–1156 (1994).

    Article  ADS  CAS  PubMed  Google Scholar 

  63. Meyers, D. A. et al. Evidence for a locus regulating total serum IgE levels mapping to chromosome 5. Genomics 23, 464– 470 (1994).

    Article  CAS  PubMed  Google Scholar 

  64. Barnes, K. C. et al. Linkage of asthma and total serum IgE concentration to markers on chromosome 12q: evidence from Afro-Caribbean and Caucasian populations. Genomics 37, 41–50 (1996).

    Article  CAS  PubMed  Google Scholar 

  65. Nickel, R. et al. Evidence for linkage of chromosome 12q15-q24. 1 markers to high total serum IgE concentrations in children of the German Multicenter Allergy Study. Genomics 46, 159– 162 (1997).

    Article  CAS  PubMed  Google Scholar 

  66. Moffatt, M. F. et al. Genetic linkage of the TCR-α/δ region to specific Immunoglobulin E responses. Lancet 343, 1597–1600 (1994).

    Article  CAS  PubMed  Google Scholar 

  67. Daniels, S. E. et al. A genome-wide search for quantitative trait loci underlying asthma. Nature 383, 247– 250 (1996).

    Article  ADS  CAS  PubMed  Google Scholar 

  68. Eiberg, H., Lind, P., Mohr, J. & Nielsen, L. S. Linkage relationship between the human immunoglobulin-E polymorphism and ESD marker. Cytogen. Cell. Genet. 40, 622 ( 1985).

    Google Scholar 

  69. Kimura, K. et al. Linkage and association of atopic asthma to markers on chromosome 13 in the Japanese population. Hum. Molec. Genet. 8 , 1487–1490 (1999).

    Article  CAS  PubMed  Google Scholar 

  70. Ober, C. et al. [The Collaborative Study on the Genetics of Asthma. ] Genome-wide search for asthma susceptibility loci in a founder population. Hum. Mol. Genet. 7, 1393–1398 (1998).

    Article  CAS  PubMed  Google Scholar 

  71. Wjst, M. et al. [German Asthma Genetics Group. ] A genome-wide search for linkage to asthma. Genomics 58, 1– 8 (1999).

    Article  CAS  PubMed  Google Scholar 

  72. Hizawa, N. et al. [The Collaborative Study on the Genetics of Asthma (CSGA). ] Genetic regulation of Dermatophagoides pteronyssinus-specific IgE responsiveness: a genome-wide multipoint linkage analysis in families recruited through 2 asthmatic sibs. J. Allergy Clin. Immunol. 102, 436–442 (1998).

    Article  CAS  PubMed  Google Scholar 

  73. The Collaborative Study on the Genetics of Asthma (CSGA). A genome-wide search for asthma susceptibility loci in ethnically diverse populations. Nature Genet. 15, 389–392 (1997).

    Article  Google Scholar 

  74. Dizier, M. H. et al. Genome screen for asthma and related phenotypes in the French EGEA study. Am. J. Respir. Crit. Care Med. 159, A649 (1999).

    Google Scholar 

  75. Satsangi, J. et al. Two stage genome-wide search in inflammatory bowel disease provides evidence for susceptibility loci on chromosomes 3, 7 and 12. Nature Genet. 14, 199–202 (1996).

    Article  CAS  PubMed  Google Scholar 

  76. Hugot, J. P. et al. Mapping of a susceptibility locus for Crohn's disease on chromosome 16. Nature 379, 821–823 (1996).

    Article  ADS  CAS  PubMed  Google Scholar 

  77. Duerr, R. H. et al. Linkage and association between inflammatory bowel disease and a locus on chromosome 12. Am. J. Hum. Genet. 63 , 95–100 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Mansfield, J. C. et al. Novel genetic association between ulcerative colitis and the anti-inflammatory cytokine interleukin-1 receptor antagonist. Gastroenterology 106, 637–642 (1994).

    Article  CAS  PubMed  Google Scholar 

  79. Hardwick, L. J. et al. Genetic mapping of susceptibility loci in the genes involved in rheumatoid arthritis. J. Rheumatol. 24, 197–198 (1997).

    CAS  PubMed  Google Scholar 

  80. Nakagawa, Y. et al. Fine mapping of the diabetes-susceptibility locus, IDDM4, on chromosome 11q13. Am. J. Hum. Genet. 63, 547–556 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Ramsay, G. DNA chips: state-of-the art. Nature Biotechnol. 16, 40–44 (1998).

    Article  CAS  Google Scholar 

  82. Risch, N. & Merikangas, K. The future of genetic studies of complex human diseases. Science 273, 1516–1517 (1996).

    Article  ADS  CAS  PubMed  Google Scholar 

  83. Moffatt, M. F. & Cookson, W. O. The genetics of asthma. Maternal effects in atopic disease. Clin. Exp. Allergy 28 (Suppl 1), 56–61 (discussion 65–66) (1998).

    Article  PubMed  Google Scholar 

  84. Warram, J. H., Krolewski, A. S., Gottlieb, M. S. & Kahn, C. R. Differences in risk of insulin-dependent diabetes in offspring of diabetic mothers and diabetic fathers. N. Engl. J. Med. 311, 149–152 (1984).

    Article  CAS  PubMed  Google Scholar 

  85. Akolkar, P. N. et al. Differences in risk of Crohn's disease in offspring of mothers and fathers with inflammatory bowel disease. Am. J. Gastroenterol. 92, 2241–2244 ( 1997).

    CAS  PubMed  Google Scholar 

  86. Koumantaki, Y. et al. Family history as a risk factor for rheumatoid arthritis: a case-control study. J. Rheumatol. 24, 1522–1526 (1997).

    CAS  PubMed  Google Scholar 

  87. Vorechovsky, I., Webster, A. D. B., Plebani, A. & Hammarstrom, L. Genetic linkage of IgA deficiency to the major histocompatibility complex: evidence for allele segregation distortion, parent-of-origin penetrance differences, and the role of IgA antibodies in disease predisposition. Am. J. Hum. Genet. 64, 1096–1109 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Hall, J. G. Genomic imprinting. Arch. Dis. Child. 65, 1013–1016 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Moffatt, M. F. et al. Factors confounding genetic linkage between atopy and chromosome 11q. Clin. Exp. Allergy 22, 1046– 1051 (1992).

    Article  CAS  PubMed  Google Scholar 

  90. Moffatt, M. F., Abecasis, G., James, A., Musk, A. W. & Cookson, W. O. C. M. Association of parental atopy phenotype with linkage to FcεRI-β. Am. J. Respir. Crit. Care Med. 159, A648 (1999).

    Google Scholar 

  91. Bennett, S. T. & Todd, J. A. Human type I diabetes and the insulin gene: principles of mapping polygenes. Annu. Rev. Genet. 30, 343–370 ( 1996).

    Article  CAS  PubMed  Google Scholar 

  92. Chess, A. Expansion of the allelic exclusion principle? Science 279, 2067–2068 (1998).

    Article  CAS  PubMed  Google Scholar 

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Cookson, W. The alliance of genes and environment in asthma and allergy. Nature 402 (Suppl 6760), 5–11 (1999). https://doi.org/10.1038/35037002

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