| http://purl.uniprot.org/citations/30215709 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/30215709 | http://www.w3.org/2000/01/rdf-schema#comment | "Birdshot Uveitis (Birdshot) is a rare eye condition that affects HLA-A29-positive individuals and could be considered a prototypic member of the recently proposed 'MHC-I (major histocompatibility complex class I)-opathy' family. Genetic studies have pinpointed the endoplasmic reticulum aminopeptidase (ERAP1) and (ERAP2) genes as shared associations across MHC-I-opathies, which suggests ERAP dysfunction may be a root cause for MHC-I-opathies. We mapped the ERAP1 and ERAP2 haplotypes in 84 Dutch cases and 890 controls. We identified association at variant rs10044354, which mediated a marked increase in ERAP2 expression. We also identified and cloned an independently associated ERAP1 haplotype (tagged by rs2287987) present in more than half of the cases; this ERAP1 haplotype is also the primary risk and protective haplotype for other MHC-I-opathies. We show that the risk ERAP1 haplotype conferred significantly altered expression of ERAP1 isoforms in transcriptomic data (n = 360), resulting in lowered protein expression and distinct enzymatic activity. Both the association for rs10044354 (meta-analysis: odds ratio (OR) [95% CI]=2.07[1.58-2.71], P = 1.24 × 10(-7)) and rs2287987 (OR[95% CI]: =2.01[1.51-2.67], P = 1.41 × 10(-6)) replicated and showed consistent direction of effect in an independent Spanish cohort of 46 cases and 2103 controls. In both cohorts, the combined rs2287987-rs10044354 haplotype associated with Birdshot more strongly than either variant alone [meta-analysis: P=3.9 × 10(-9)]. Finally, we observed that ERAP2 protein expression is dependent on the ERAP1 background across three European populations (n = 3353). In conclusion, a functionally distinct combination of ERAP1 and ERAP2 are a hallmark of Birdshot and provide rationale for strategies designed to correct ERAP function for treatment of Birdshot and MHC-I-opathies more broadly."xsd:string |
| http://purl.uniprot.org/citations/30215709 | http://purl.org/dc/terms/identifier | "doi:10.1093/hmg/ddy319"xsd:string |
| http://purl.uniprot.org/citations/30215709 | http://purl.uniprot.org/core/author | "Martin J."xsd:string |
| http://purl.uniprot.org/citations/30215709 | http://purl.uniprot.org/core/author | "Hoyng C.B."xsd:string |
| http://purl.uniprot.org/citations/30215709 | http://purl.uniprot.org/core/author | "Missotten T.O.A.R."xsd:string |
| http://purl.uniprot.org/citations/30215709 | http://purl.uniprot.org/core/author | "Reeves E."xsd:string |
| http://purl.uniprot.org/citations/30215709 | http://purl.uniprot.org/core/author | "James E."xsd:string |
| http://purl.uniprot.org/citations/30215709 | http://purl.uniprot.org/core/author | "Ophoff R.A."xsd:string |
| http://purl.uniprot.org/citations/30215709 | http://purl.uniprot.org/core/author | "Den Hollander A.I."xsd:string |
| http://purl.uniprot.org/citations/30215709 | http://purl.uniprot.org/core/author | "Adan A."xsd:string |
| http://purl.uniprot.org/citations/30215709 | http://purl.uniprot.org/core/author | "Koeleman B.P.C."xsd:string |
| http://purl.uniprot.org/citations/30215709 | http://purl.uniprot.org/core/author | "Hiddingh S."xsd:string |
| http://purl.uniprot.org/citations/30215709 | http://purl.uniprot.org/core/author | "Marquez A."xsd:string |
| http://purl.uniprot.org/citations/30215709 | http://purl.uniprot.org/core/author | "Fonollosa A."xsd:string |
| http://purl.uniprot.org/citations/30215709 | http://purl.uniprot.org/core/author | "Pulit S.L."xsd:string |
| http://purl.uniprot.org/citations/30215709 | http://purl.uniprot.org/core/author | "Cordero-Coma M."xsd:string |
| http://purl.uniprot.org/citations/30215709 | http://purl.uniprot.org/core/author | "Radstake T.R.D.J."xsd:string |
| http://purl.uniprot.org/citations/30215709 | http://purl.uniprot.org/core/author | "Kuiper J.J.W."xsd:string |
| http://purl.uniprot.org/citations/30215709 | http://purl.uniprot.org/core/author | "Boer J.H."xsd:string |
| http://purl.uniprot.org/citations/30215709 | http://purl.uniprot.org/core/author | "Cretu-Stancu M."xsd:string |
| http://purl.uniprot.org/citations/30215709 | http://purl.uniprot.org/core/author | "Devall M."xsd:string |
| http://purl.uniprot.org/citations/30215709 | http://purl.uniprot.org/core/author | "Setten J.V."xsd:string |
| http://purl.uniprot.org/citations/30215709 | http://purl.uniprot.org/core/author | "Velthoven M.V."xsd:string |
| http://purl.uniprot.org/citations/30215709 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |