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.