Find in Library

Epistasis of <i>ERAP1</i> single nucleotide variations (SNVs) and <i>HLA-B27</i> has been linked to ankylosing spondylitis susceptibility (AS). The current study examined how prevalent <i>ERAP1</i> allelic variants (SNV haplotypes) in Taiwan affect ERAP1 functions and AS susceptibility in the presence or absence of HLA-B27. Sanger sequencing was used to discover all <i>ERAP1</i> coding SNVs and common allelic variants in Taiwanese full-length cDNAs from 45 human patients. For the genetic association investigation, TaqMan genotyping assays were utilized to establish the genotypes of <i>ERAP1</i> SNVs in 863 AS patients and 1438 healthy controls. Ex vivo biological analysis of peripheral blood mononuclear cells from homozygous donors of two common-risk <i>ERAP1</i> allelic variants was performed. Two common-risk <i>ERAP1</i> allelic variants were also cloned and functionally studied. In Taiwanese, eleven frequent <i>ERAP1</i> SNVs and six major <i>ERAP1</i> allelic variants were discovered. We discovered that in Taiwanese, the most prevalent <i>ERAP1</i>-001 variant with 56E, 127R, 276I, 349M, 528K, 575D, 725R, and 730Q interacting with <i>HLA-B27</i> significantly contributed to the development of AS. In <i>HLA-B27</i> negative group, however, the second most prevalent <i>ERAP1</i>-002 variant with 56E, 127P, 276M, 349M, 528R, 575D, 725R, and 730E was substantially related with an increased risk of AS. Ex vivo and in vitro research demonstrated that <i>ERAP1</i> allelic variants have a significant impact on ERAP1 functions, suggesting that ERAP1 plays a role in the development of AS. In an HLA-B27-dependent manner, common <i>ERAP1</i> allelic variants are related with AS susceptibility.