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


OBJECTIVE
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.
Melén
Erik
E
Institute of Environmental Medicine, Centre for Allergy Research, and Department of Biosciences, Karolinska Institutet, Box 210, Stockholm SE-171 77, Sweden.
Bruce
Sara
S
Doekes
Gert
G
Kabesch
Michael
M
Laitinen
Tarja
T
Lauener
Roger
R
Lindgren
Cecilia M
CM
Riedler
Josef
J
Scheynius
Annika
A
van Hage-Hamsten
Marianne
M
Kere
Juha
J
Pershagen
Göran
G
Wickman
Magnus
M
Nyberg
Fredrik
F
D000293:Adolescent; D017677:Age Distribution; D001249:Asthma / Q000453:epidemiology / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003233:Conjunctivitis, Allergic / Q000235:genetics; D003430:Cross-Sectional Studies; D005060:Europe / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology* / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D015995:Prevalence; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D012221:Rhinitis, Allergic, Perennial / Q000453:epidemiology / Q000235:genetics; D017678:Sex Distribution
D043562:Receptors, G-Protein-Coupled