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

Am J Respir Crit Care Med. 2005 May 15;171(10):1089-95. doi: 10.1164/rccm.200410-1317OC. Epub 2005 Feb 11.


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 > or = 0.35 kU/L, p = 0.022), with significant haplotype-specific associations for H1, H5, 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Distribution
  • Asthma / epidemiology
  • Asthma / genetics
  • Child
  • Child, Preschool
  • Cohort Studies
  • Conjunctivitis, Allergic / genetics
  • Cross-Sectional Studies
  • Europe / epidemiology
  • Female
  • Genetic Predisposition to Disease / epidemiology*
  • Genetic Predisposition to Disease / genetics*
  • Haplotypes / genetics*
  • Humans
  • Hypersensitivity, Immediate / epidemiology*
  • Hypersensitivity, Immediate / genetics*
  • Male
  • Polymorphism, Genetic / genetics
  • Prevalence
  • Receptors, G-Protein-Coupled / genetics*
  • Rhinitis, Allergic, Perennial / epidemiology
  • Rhinitis, Allergic, Perennial / genetics
  • Sex Distribution


  • Receptors, G-Protein-Coupled