Variations in the CCL20 and CCR6 Genes are Associated with Atopic Dermatitis and Eczema Herpeticum in Populations of European and African descent.

Abstract

RATIONALE: Atopic dermatitis (AD) can be complicated by disseminated viral skin infections including HSV leading to eczema herpeticum (ADEH), or vaccinia leading to eczema vaccinatum (EV). CCL20 is produced by keratinocytes and its deficiency in AD skin may explain susceptibility to ADEH or EV. Expression of CCL20 receptor, CCR6, is also decreased in AD. Collectively, CCL20 and CCR6 represent attractive candidate genes for AD, ADEH and EV. METHODS: Using Illumina BeadXpress and Taqman tools, we genotyped seven single nucleotide polymorphisms (SNPs) for CCL20 and eight SNPs for CCR6, in European American (EA; N = 321) and African American (AA; N = 307) patients and healthy controls. An additional group of 83 EA and 16 AA patients with ADEH were also genotyped. Genetic associations were determined by Cochran-Armitage trend test using PLINK. RESULTS: Among the EA group, the promoter SNP, rs13034664, in CCL20 was significantly associated with AD (P = 0.002), and AD combined with ADEH subjects (P = 0.0009). A flanking SNP (rs3138119) was significantly associated with ADEH in the AA group (P = 0.03), and the SNP, rs940339, was associated with ADEH in the EA group (P = 0.01). A two-SNP (AG) haplotype (rs13034664, rs3138119) was associated with AD (P = 0.001) in the EA group. A gene-gene interaction in the EA population for the AD phenotype was observed between rs13034664 in CCL20 and intronic SNP, rs3093010, of CCR6 (P = 0.009). CONCLUSIONS: Results from this study suggest that variants in CCL20 and CCR6 are relevant to AD, and provide first replicated evidence for association between CCL20 variants and risk of severe viral complications in AD, such as ADEH.