Haplotypes of G protein-coupled receptor 154 are associated with childhood allergy and asthma

Erik Melén, Sara Bruce, Gert Doekes, Michael Kabesch, Tarja Laitinen, Roger Lauener, Cecilia M. Lindgren, Josef Riedler, Annika Scheynius, Marianne Van Hage-Hamsten, Juha Kere, Göran Pershagen, Magnus Wickman, Fredrik Nyberg, Charlotte Braun-Fahrländer, Marco Waser, Bert Brunekreef, Dieneke Schram, Erika Von Mutius, Marcus EgeErik Melén, Fernando Martinez

Research output: Contribution to journalArticle

91 Scopus citations

Abstract

Rationale: Allergic diseases are influenced by both genes and environment. A 70-kb haplotype block in the G protein-coupled receptor for asthma susceptibility gene (GPR154; alias GPRA) on chromosome 7p was recently identified to influence susceptibility to asthma and elevated total serum IgE levels in adults. Objectives: To assess the impact of GPR154 on childhood allergic disease, including allergic sensitization, asthma, and rhinoconjunctivitis, in study populations with diverse environmental backgrounds. Methods: We studied farm children, Steiner school children, and two reference groups from five Western European countries in the cross-sectional PARSIFAL (Prevention of Allergy Risk factors for Sensitization In children related to Farming and Anthroposophic Lifestyle) study and a sample of children from the Swedish birth cohort study BAMSE. DNA samples from 3,113 PARSIFAL and 800 BAMSE children were genotyped for 7 GPR154 polymorphisms and haplotypes were inferred. The proportions of alleles and haplotypes (H1-H7) were compared in affected children with their healthy counterparts. Results: Data indicate a global association of the haplotype block to sensitization (allergen-specific serum IgE ≥ 0.35 kU/L, p = 0.022), with significant haplotype-specific associations for H1, H7, and H6. Haplotypes H1 and H5 were also significantly associated with childhood allergic asthma (p = 0.045 and p = 0.023, respectively), and H5 to asthma regardless of sensitization. A broader involvement of GPR154 in allergic diseases was further supported in allergic rhinoconjunctivitis (H3: p = 0.046). The associated haplotypes could be allocated into risk (H5/H6) and nonrisk (H1/H3) groups, a pattern supported by allelic association of single nucleotide polymorphisms (SNPs) rs324384 and rs324396. Conclusions: Our results indicate that polymorphisms and haplotypes in the haplotype block of GPR154 are associated with asthma, rhinoconjunctivitis, and sensitization in European children.

Original languageEnglish (US)
Pages (from-to)1089-1095
Number of pages7
JournalAmerican journal of respiratory and critical care medicine
Volume171
Issue number10
DOIs
StatePublished - May 15 2005
Externally publishedYes

Keywords

  • Asthma
  • Children
  • GPRA gene
  • Genetic association
  • IgE

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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    Melén, E., Bruce, S., Doekes, G., Kabesch, M., Laitinen, T., Lauener, R., Lindgren, C. M., Riedler, J., Scheynius, A., Van Hage-Hamsten, M., Kere, J., Pershagen, G., Wickman, M., Nyberg, F., Braun-Fahrländer, C., Waser, M., Brunekreef, B., Schram, D., Von Mutius, E., ... Martinez, F. (2005). Haplotypes of G protein-coupled receptor 154 are associated with childhood allergy and asthma. American journal of respiratory and critical care medicine, 171(10), 1089-1095. https://doi.org/10.1164/rccm.200410-1317OC