Synergy of endoplasmic reticulum aminopeptidase 1 and 2 (ERAP1 and ERAP2) polymorphisms in atopic dermatitis: Effects on disease prevalence.

Endoplasmic reticulum aminopeptidases ERAP1 and ERAP2 trim peptides to a length of 8-10 amino acids optimal for binding by HLA class I molecules. Although these two enzymes may work separately, but they may also form a heterodimer of enhanced trimming efficiency. We have earlier described a role for ERAP1 single nucleotide polymorphism rs26618 and HLA-C05:01 as risk factors for atopic dermatitis (AD). Here, we examined whether ERAP2 single nucleotide polymorphism rs2248374, determining the presence or absence of the functional form of enzyme, would influence the rs26618 effect. Out of nine rs2248374 - rs26618 genotypic combinations, only one, rs2248374A/A - rs26618C/C, was associated with a risk of AD. Interestingly, the odds ratio increased from 1.10 (CI95%: 0.72; 1.69; p = 0.657) for ERAP2 rs2248374A/A and 1.88 (CI95%: 1.07; 3.28; p = 0.025) for ERAP1 rs26618*C/C to 3.36 (CI95%: 1.41; 8.01; p = 0.004) for their combination, therefore revealing a synergistic effect.