Genetic variation in CRTh2 influences development of allergic phenotypes.
BACKGROUND
Allergic disorders are characterized by an increase in the Th2 cytokines IL-4, IL-5 and IL-13, produced primarily by Th2 cells. These cells are marked by the expression of CRTh2 (chemoattractant receptor-homologous molecule expressed on Th2 cells), a receptor for prostaglandin D(2). As genetic variation plays a significant role in the predisposition for allergic disorders, we investigated the influence of single nucleotide polymorphisms (SNPs) in CRTh2.


METHODS
In a large study population of German children (n = 4264) from the International Study of Asthma and Allergy in Children (ISAAC II), six polymorphisms in CRTh2 were genotyped. Statistical analyses were performed using single SNP and haplotype analyses.


RESULTS
Uncorrected associations among -6373G>A, +1431G>C and +1538A>G were observed with a number of allergic phenotypes (P < 0.05). After correction, association between +1431C and specific IgE to food allergens remained significant (P = 0.04). Associations of haplotype (H)3 (containing +1538G) with reduced risk for asthma and H2 (containing +1431C) with increased risk for specific IgE to food allergens also remained significant after correction for multiple testing (P = 0.004).


CONCLUSIONS
Genetic variation within CRTh2 modifies the development of allergic sensitization and asthma in a population of German children.
Cameron
L
L
Pulmonary Research Group, University of Alberta, Edmonton, Canada.
Depner
M
M
University Children's Hospital, Ludwig Maximillian's University, Munich, Germany.
Kormann
M
M
University Children's Hospital, Ludwig Maximillian's University, Munich, Germany.
Klopp
N
N
Institute of Epidemiology, GSF - Research Centre for Environment and Health, Neuherberg, Germany.
Illig
T
T
Institute of Epidemiology, GSF - Research Centre for Environment and Health, Neuherberg, Germany.
Von Mutius
E
E
University Children's Hospital, Ludwig Maximillian's University, Munich, Germany.
Kabesch
M
M
Department of Pediatric Pneumology and Neonatology, Medical School Hannover, Hannover, Germany.
D001249:Asthma / Q000235:genetics / Q000503:physiopathology; D002648:Child; D003430:Cross-Sectional Studies; D004485:Eczema / Q000235:genetics / Q000503:physiopathology; D005512:Food Hypersensitivity / Q000235:genetics / Q000503:physiopathology; D014644:Genetic Variation; D005838:Genotype; D005858:Germany; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics* / Q000503:physiopathology*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011971:Receptors, Immunologic / Q000235:genetics*; D011982:Receptors, Prostaglandin / Q000235:genetics*; D012135:Respiratory Sounds / Q000235:genetics / Q000503:physiopathology; D006255:Rhinitis, Allergic, Seasonal / Q000235:genetics / Q000503:physiopathology
D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; C036293:prostaglandin D2 receptor