The association of ERAP1 and ERAP2 single nucleotide polymorphisms and their haplotypes with psoriasis vulgaris is dependent on the presence or absence of the HLA-C*06:02 allele and age at disease onset

The aim of this case-control study was to elucidate the role of some single nucleotide polymorphisms (SNPs) in the ERAP1 (rs27524, rs27044, rs30187, rs2287987 and rs26653) and ERAP2 (rs2248374) genes in predicting the risk for psoriasis vulgaris in the Polish population. ERAP1, ERAP2 and HLA-C*06:02 typing was done using the TaqMan SNP genotyping assays. We confirmed a strong association of the HLA-C*06:02 allele with early-onset psoriasis. In ERAP1, rs30187T increased the risk of psoriasis in HLA-C*06:02-positive patients, most strongly in late onset psoriasis, whereas it was protective when the HLA-C*06:02 allele was absent. We also found a protective effect of the ERAP2 rs2248374A allele and rs2248374AA genotype only in HLA-C*06:02 carriers, especially in the subgroup of patients with juvenile psoriasis. Analysis of combined haplotypes for ERAP1 and ERAP2 also revealed differences when the patients and controls were stratified by HLA-C*06:02. An ERAP1 haplotype known to possess high enzymatic activity was associated with psoriasis if HLA-C*06:02 was present and a functional ERAP2 allele was absent. In the absence of HLA-C*06:02, an ERAP1 haplotype of low activity was conducive to psoriasis if a functional ERAP2 allele was present, but the same ERAP1 haplotype was protective if the ERAP2 allele was defective.