The genetics of asthma and allergic disease: a 21st century perspective

Immunol Rev. 2011 Jul;242(1):10-30. doi: 10.1111/j.1600-065X.2011.01029.x.

Abstract

Asthma and allergy are common conditions with complex etiologies involving both genetic and environmental contributions. Recent genome-wide association studies (GWAS) and meta-analyses of GWAS have begun to shed light on both common and distinct pathways that contribute to asthma and allergic diseases. Associations with variation in genes encoding the epithelial cell-derived cytokines, interleukin-33 (IL-33) and thymic stromal lymphopoietin (TSLP), and the IL1RL1 gene encoding the IL-33 receptor, ST2, highlight the central roles for innate immune response pathways that promote the activation and differentiation of T-helper 2 cells in the pathogenesis of both asthma and allergic diseases. In contrast, variation at the 17q21 asthma locus, encoding the ORMDL3 and GSDML genes, is specifically associated with risk for childhood onset asthma. These and other genetic findings are providing a list of well-validated asthma and allergy susceptibility genes that are expanding our understanding of the common and unique biological pathways that are dysregulated in these related conditions. Ongoing studies will continue to broaden our understanding of asthma and allergy and unravel the mechanisms for the development of these complex traits.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Asthma / epidemiology
  • Asthma / genetics*
  • Asthma / immunology
  • Asthma / metabolism
  • Child
  • Chromosomes, Human, Pair 17
  • Cytokines / genetics
  • Cytokines / metabolism
  • Gene Expression Regulation / immunology*
  • Genetic Linkage
  • Genetic Loci
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genome-Wide Association Study / trends
  • Humans
  • Hypersensitivity, Immediate / epidemiology
  • Hypersensitivity, Immediate / genetics*
  • Hypersensitivity, Immediate / immunology
  • Hypersensitivity, Immediate / metabolism
  • Immunity, Innate
  • Infant
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukins / genetics
  • Interleukins / metabolism
  • Lymphocyte Activation
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Meta-Analysis as Topic
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Th2 Cells / immunology*
  • Th2 Cells / metabolism
  • Thymic Stromal Lymphopoietin

Substances

  • Cytokines
  • GSDMB protein, human
  • IL1RL1 protein, human
  • IL33 protein, human
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukins
  • Membrane Proteins
  • Neoplasm Proteins
  • ORMDL3 protein, human
  • Receptors, Cell Surface
  • Thymic Stromal Lymphopoietin