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Am J Respir Crit Care Med. 2005 May 15;171(10):1089-95. Epub 2005 Feb 11.

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

Author information

1
Institute of Environmental Medicine, Centre for Allergy Research, and Department of Biosciences, Karolinska Institutet, Box 210, Stockholm SE-171 77, Sweden.

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 > 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.

Comment in

PMID:
15710598
DOI:
10.1164/rccm.200410-1317OC
[Indexed for MEDLINE]

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