Association of CARD15 polymorphisms with atopy-related traits in a population-based cohort of Caucasian adults

Background: Influences of microbial pathogens are crucial for the maturation of the immune system. Caspase-recruitment domain containing protein 15 (CARD 15) is a cytosolic receptor involved in bacterial recognition by antigen-presenting cells. CARD15 polymorphisms have been associated with Crohn's disease. Recently, associations with atopic phenotypes have been reported in children. Objective: Within a large population of German adults (n = 1875), we evaluated eight CARD15 polymorphisms for associations with atopic phenotypes. Methods: Subjects were phenotyped by standardized questionnaires and interviews as well as total and allergen-specific IgE measurements. Genotyping was performed using matrix-assisted laser desorption ionization - time of flight mass spectrometry. Haplotypes were estimated using the SAS/Genetics module. Results: Subjects with a T allele at rs1077861 had a decreased risk of developing asthma (odds ratio OR = 0.648, P = 0.013), whereas the presence of an A allele at rs3135500 was significantly associated with an increased risk (OR = 1.374, P = 0.023). In addition, a CARD15 haplotype revealed to be protective against the development of asthma (OR = 0.326, P = 0.003). Subjects with an A allele at position rs5743266 or a T allele at rs2066842 had a significantly decreased risk of developing allergic rhinoconjunctivitis with ORs of 0.820 (P = 0.049) and 0.801 (P = 0.025). Polymorphism rs2066845 showed a significant association with increased total serum IgE (OR = 2.155, P = 0.006). Conclusion: Genetic variants of CARD15 that might result in inappropriate immunomodulation are not only associated with autoimmune diseases but also with atopic disorders.