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Previous studies have suggested that variants in the protocadherin-1 (PCDH1) gene, which is important for cell-cell adhesion, are associated with asthma, bronchial, hyperresponsiveness and atopic dermatitis in school children. Our aim was to associate common variants of the PCDH1 gene with longitudinally assessed asthma phenotypes and atopic dermatitis in early childhood. We analysed eight single-nucleotide polymorphisms in PCDH1 from 411 children born to asthmatic mothers from the Copenhagen Prospective Studies on Asthma in Childhood birth cohort. Asthma and atopic dermatitis were diagnosed prospectively to the age of 7 years and asthma was categorised by temporal pattern: transient early respiratory symptoms, persistent symptoms and late-onset symptoms. Bronchial responsiveness was measured at age 6 years. We used additive genetic models. Kaplan-Meier plots revealed early onset in hetero- and homozygotes for the rs10063472-T allele. Significant association was observed between the transient early phenotype and rs10063472-T (transient early versus all: OR 1.91, 95% CI 1.21-3.01, p=0.0058; transient early versus asymptomatic: OR 2.00, 95% CI 1.23-3.25, p=0.0053). No association was observed for other symptom patterns or bronchial responsiveness. Significant association was observed for atopic dermatitis and rs11167761-A (OR 1.85, 95% CI 1.24-2.75, p=0.0026). Common variations in PCDH1 increase the risk of developing both transient early asthma and atopic dermatitis in early childhood.

The PCDH1 gene and asthma in early childhood