SPINK5 is associated with early-onset and CHI3L1 with late-onset atopic dermatitis.

Abstract

We have recently showed that filaggrin (FLG) mutations are associated only with early-onset of AD, but not with late-onset of AD. Consequently, other susceptibility genes should receive attention, especially in patients with late-onset of AD. Our aim was to assess the associations between development of AD and the polymorphisms rs2303067 in SPINK5 and rs490928 in CHI3L1. A study population of 241 AD patients and 164 healthy controls was genotyped for two polymorphisms (rs2303067 in SPINK5 and rs490928 in CHI3L1). Rs2303067 in SPINK5 was significantly associated with early-onset AD (≤8years: p=.003; OR=2.57) and was characterized by the need for hospitalization (p=.006; OR=2.76), prolonged duration (≥10years; p=.008; OR=2.32) and more body parts affected (p=.015; OR=2.01). In contrast, rs490928 in CHI3L1 was associated with late-onset AD (>8years: p=.048; OR=1.65) and was characterized by no need for hospitalization (p=.049; OR=1.59), shorter duration (<10years; p=.017; OR=1.94) and fewer body parts affected (p=.049; OR=1.75). Our results confirmed that different AD phenotypes, specifically early- and late-onset AD, have different genetic backgrounds. Early-onset AD was associated with rs2303067 in SPINK5, which is involved in skin barrier functioning, and late-onset was associated with rs4950928 in CHI3L1, which is involved in the immune response. Future studies should examine the early- versus late-onset subgrouping more closely.