Functional polymorphisms in ERAP1 and ERAP2 genes have been associated with predisposition to several diseases including autoimmune diseases, viral infections, and virally induced cancers.
In this article, we review the distribution of ERAP1 and ERAP2 gene polymorphisms in various populations; discuss the risk or protective influence of these gene polymorphisms in autoimmune diseases, infectious diseases, and cancers; and highlight how ERAP genetic variations can influence disease associations.
This review focuses on the ambivalent role of HLA-B27 in autoimmunity and viral protection correlating its functions to the quantitative and qualitative effects of ERAP1 and ERAP2 polymorphisms on their enzymatic activity.
Recent evidence has suggested that the activity of ERAP2 may contribute to the generation of autoimmunity, thus making ERAP2 a possible pharmacological target for the regulation of adaptive immune responses.
Our study therefore reveals the fine-mapped AID risk variants that act as eQTLs with ERAP2 in thymus, and highlights the potential causal regulatory variants.
A functional polymorphism in the gene (rs30187, rs30187" genes_norm="51752">Arg528Lys) associates with susceptibility to ankylosying spondylitis (AS), whereas a SNP in the interacting ERAP2 gene increases susceptibility to another inflammatory autoimmune disorder, Crohn's disease (CD).