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-C*05:01 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, rs2248374*A/A – rs26618*C/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 rs2248374*A/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.

内质网氨肽酶 ERAP1 和 ERAP2 将肽段修剪为 8-10 个氨基酸的长度，最适合与 HLA I 类分子结合。虽然这两种酶可能单独工作，但它们也可能形成修剪效率增强的异源二聚体。我们之前已经描述了ERAP1单核苷酸多态性rs26618和HLA-C*05:01作为特应性皮炎 (AD) 危险因素的作用。在这里，我们检查了ERAP2单核苷酸多态性rs2248374，确定酶的功能形式的存在与否，是否会影响rs26618效应。九个rs2248374 – rs26618基因型组合，只有一个，rs2248374*A/A – rs26618*C/C，与 AD 风险相关。有趣的是，比值比从1.10升高（CI95％：0.72; 1.69; P = 0.657），用于ERAP2 rs2248374 * A / A和1.88（CI95％：1.07; 3.28; P = 0.025），用于ERAP1 rs26618 * C / C 3.36 (CI95%: 1.41; 8.01; p = 0.004) 它们的组合，因此揭示了协同效应。