TY - JOUR
T1 - Haplotypes of G protein-coupled receptor 154 are associated with childhood allergy and asthma
AU - Melén, Erik
AU - Bruce, Sara
AU - Doekes, Gert
AU - Kabesch, Michael
AU - Laitinen, Tarja
AU - Lauener, Roger
AU - Lindgren, Cecilia M.
AU - Riedler, Josef
AU - Scheynius, Annika
AU - Van Hage-Hamsten, Marianne
AU - Kere, Juha
AU - Pershagen, Göran
AU - Wickman, Magnus
AU - Nyberg, Fredrik
AU - Braun-Fahrländer, Charlotte
AU - Waser, Marco
AU - Brunekreef, Bert
AU - Schram, Dieneke
AU - Von Mutius, Erika
AU - Ege, Marcus
AU - Melén, Erik
AU - Martinez, Fernando
PY - 2005/5/15
Y1 - 2005/5/15
N2 - 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.
AB - 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.
KW - Asthma
KW - Children
KW - GPRA gene
KW - Genetic association
KW - IgE
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U2 - 10.1164/rccm.200410-1317OC
DO - 10.1164/rccm.200410-1317OC
M3 - Article
C2 - 15710598
AN - SCOPUS:20844448390
SN - 1073-449X
VL - 171
SP - 1089
EP - 1095
JO - American journal of respiratory and critical care medicine
JF - American journal of respiratory and critical care medicine
IS - 10
ER -