Exploring associations of single nucleotide polymorphisms in ERAP1 and ERAP2 with susceptibility to multiple...

Single nucleotide polymorphisms (SNPs) in the endoplasmic reticulum aminopeptidase 1 (ERAP1) and ERAP2 genes have been associated with susceptibility to various immune-mediated inflammatory diseases (IMIDs). We utilized a unique cohort from the National Centre for Autoimmune Diseases (NCAS) to investigate whether specific SNPs in ERAP1 and ERAP2 act as a shared genetic susceptibility factor across various IMIDs. The study population comprised 171 patients from the NCAS cohort with two or more IMIDs and 57 healthy controls. Using real-time PCR allelic discrimination methods, we genotyped specific SNPs in ERAP1 (rs30187, rs27524), ERAP2 (rs2248374) and HLA-C (rs4406273). The distribution of ERAP1 and ERAP2 risk/minor alleles, genotypes and haplotypes was similar in the NCAS cohort and in healthy controls. When stratifying for HLA-C*06:02 positive psoriasis patients, a disease-associated haplotype A-A-T (rs2248374, rs27524, rs30187) was identified, significantly increasing the odds for having psoriasis and one or more IMIDs (OR = 3.41, 95 % CI: 1.32 - 8.78, p = 0.008). While SNPs in ERAP1 and ERAP2 may not constitute a shared susceptibility factor across all IMIDs, this study suggests a complex interaction between HLA types, ERAP1, and ERAP2, potentially influencing the development of certain MHC-I-associated disorders.