A rare variant in CYP27A1 and its association with atopic dermatitis with high serum total IgE.

This study investigated rare variants associated with atopic dermatitis. We performed exome analyses on 37 patients who were diagnosed with atopic dermatitis by board-certified dermatologists and had total serum IgE levels greater than 1000 IU/ml. The exome analysis identified seven variants with <1% allele frequency in Asian (ASN) population of 1000 Genomes Project phase 1 data and >5% allele frequency in the atopic dermatitis exome samples. We then conducted a replication study using 469 atopic dermatitis patients with total serum IgE ≥1000 IU/ml and 935 Japanese controls to assess the presence of these 7 candidate variants. The replication study confirmed that CYP27A1 rs199691576 (A/G) was associated with atopic dermatitis with high serum IgE levels (P = 0.012, odds ratio = 2.1). CYP27A1 is involved in the metabolism of vitamin D3, which plays important roles in modulating immune function. Previous studies have reported polymorphisms in vitamin D pathway genes that are associated with allergy-related phenotypes. Our data confirm the importance of genes regulating the vitamin D pathway in the development of atopic dermatitis.