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The Endoplasmatic Reticulum Aminopeptidases  ERAP1  and  ERAP2  are implicated in a variety of immune and non-immune functions. Most studies however have focused on their role in shaping the HLA class I peptidome by trimming peptides to the optimal size. Genome Wide Association Studies highlighted non-synonymous polymorphisms in their coding regions as associated with several immune mediated diseases. The two genes lie contiguous and oppositely oriented on the 5q15 chromosomal region. Very little is known about the transcriptional regulation and the quantitative variations of these enzymes. Here, we correlated the level of transcripts and proteins of the two aminopeptidases in B-lymphoblastoid cell lines from 44 donors harbouring allelic variants in the intergenic region between  ERAP1  and  ERAP2 . We found that the presence of a G instead of an A at SNP rs75862629 in the  ERAP2  gene promoter strongly influences the expression of the two ERAPs with a down-modulation of  ERAP2  coupled with a significant higher expression of  ERAP1 . We therefore show here for the first time a coordinated quantitative regulation of the two  ERAP  genes, which can be relevant for the setting of specific therapeutic approaches.

An allelic variant in the intergenic region between ERAP1 and ERAP2 correlates with an inverse expression of the two genes