{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1361137045047413632.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1186/s13075-015-0692-4"}},{"identifier":{"@type":"URI","@value":"https://link.springer.com/content/pdf/10.1186/s13075-015-0692-4.pdf"}},{"identifier":{"@type":"URI","@value":"https://link.springer.com/article/10.1186/s13075-015-0692-4/fulltext.html"}},{"identifier":{"@type":"URI","@value":"http://link.springer.com/content/pdf/10.1186/s13075-015-0692-4"}}],"dc:title":[{"@value":"Association of HLA-DRB1 amino acid residues with giant cell arteritis: genetic association study, meta-analysis and geo-epidemiological investigation"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Abstract</jats:title><jats:sec>\n                        <jats:title>Introduction</jats:title>\n                        <jats:p>Giant cell arteritis (GCA) is an autoimmune disease commonest in Northern Europe and Scandinavia. Previous studies report various associations with <jats:italic>HLA-DRB1*</jats:italic>04 and <jats:italic>HLA-DRB1</jats:italic>*01; <jats:italic>HLA-DRB1</jats:italic> alleles show a gradient in population prevalence within Europe. Our aims were (1) to determine which amino acid residues within <jats:italic>HLA-DRB1</jats:italic> best explained <jats:italic>HLA-DRB1</jats:italic> allele susceptibility and protective effects in GCA, seen in UK data combined in meta-analysis with previously published data, and (2) to determine whether the incidence of GCA in different countries is associated with the population prevalence of the <jats:italic>HLA-DRB1</jats:italic> alleles that we identified in our meta-analysis.</jats:p>\n                     </jats:sec><jats:sec>\n                        <jats:title>Methods</jats:title>\n                        <jats:p>GCA patients from the UK GCA Consortium were genotyped by using single-strand oligonucleotide polymerization, allele-specific polymerase chain reaction, and direct sequencing. Meta-analysis was used to compare and combine our results with published data, and public databases were used to identify amino acid residues that may explain observed susceptibility/protective effects. Finally, we determined the relationship of <jats:italic>HLA-DRB1</jats:italic>*04 population carrier frequency and latitude to GCA incidence reported in different countries.</jats:p>\n                     </jats:sec><jats:sec>\n                        <jats:title>Results</jats:title>\n                        <jats:p>In our UK data (225 cases and 1378 controls), <jats:italic>HLA-DRB1*</jats:italic>04 carriage was associated with GCA susceptibility (odds ratio (OR) = 2.69, <jats:italic>P</jats:italic> = 1.5×10<jats:sup>−11</jats:sup>), but <jats:italic>HLA-DRB1*</jats:italic>01 was protective (adjusted OR = 0.55, <jats:italic>P</jats:italic> = 0.0046). In meta-analysis combined with 14 published studies (an additional 691 cases and 4038 controls), protective effects were seen from HLA-DR2, which comprises <jats:italic>HLA-DRB1</jats:italic>*15 and <jats:italic>HLA-DRB1</jats:italic>*16 (OR = 0.65, <jats:italic>P</jats:italic> = 8.2×10<jats:sup>−6</jats:sup>) and possibly from <jats:italic>HLA-DRB1</jats:italic>*01 (OR = 0.73, <jats:italic>P</jats:italic> = 0.037). GCA incidence (<jats:italic>n</jats:italic> = 17 countries) was associated with population <jats:italic>HLA-DRB1</jats:italic>*04 allele frequency (<jats:italic>P</jats:italic> = 0.008; adjusted R<jats:sup>2</jats:sup> = 0.51 on univariable analysis, adjusted R<jats:sup>2</jats:sup> = 0.62 after also including latitude); latitude also made an independent contribution.</jats:p>\n                     </jats:sec><jats:sec>\n                        <jats:title>Conclusions</jats:title>\n                        <jats:p>We confirm that <jats:italic>HLA-DRB1</jats:italic>*04 is a GCA susceptibility allele. The susceptibility data are best explained by amino acid risk residues V, H, and H at positions 11, 13, and 33, contrary to previous suggestions of amino acids in the second hypervariable region. Worldwide, GCA incidence was independently associated both with population frequency of <jats:italic>HLA-DRB1</jats:italic>*04 and with latitude itself. We conclude that variation in population <jats:italic>HLA-DRB1</jats:italic>*04 frequency may partly explain variations in GCA incidence and that <jats:italic>HLA-DRB1</jats:italic>*04 may warrant investigation as a potential prognostic or predictive biomarker.</jats:p>\n                     </jats:sec>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1381137045047413634","@type":"Researcher","foaf:name":[{"@value":"Sarah Louise Mackie"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137045047413633","@type":"Researcher","foaf:name":[{"@value":"John C. Taylor"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137045047413643","@type":"Researcher","foaf:name":[{"@value":"Lubna Haroon-Rashid"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137045047413636","@type":"Researcher","foaf:name":[{"@value":"Stephen Martin"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137045047413638","@type":"Researcher","foaf:name":[{"@value":"Bhaskar Dasgupta"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137045047413640","@type":"Researcher","foaf:name":[{"@value":"Andrew Gough"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137045047413635","@type":"Researcher","foaf:name":[{"@value":"Michael Green"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137045047413642","@type":"Researcher","foaf:name":[{"@value":"Lesley Hordon"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137045047413632","@type":"Researcher","foaf:name":[{"@value":"Stephen Jarrett"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137045047413637","@type":"Researcher","foaf:name":[{"@value":"Colin T. Pease"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137045047413644","@type":"Researcher","foaf:name":[{"@value":"Jennifer H. Barrett"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137045047413639","@type":"Researcher","foaf:name":[{"@value":"Richard Watts"}]},{"@id":"https://cir.nii.ac.jp/crid/1381137045047413641","@type":"Researcher","foaf:name":[{"@value":"Ann W. Morgan"}]}],"publication":{"publicationIdentifier":[{"@type":"EISSN","@value":"14786354"}],"prism:publicationName":[{"@value":"Arthritis Research & Therapy"}],"dc:publisher":[{"@value":"Springer Science and Business Media LLC"}],"prism:publicationDate":"2015-07-30","prism:volume":"17","prism:number":"1","prism:startingPage":"195"},"reviewed":"false","dc:rights":["https://creativecommons.org/licenses/by/4.0","https://creativecommons.org/licenses/by/4.0"],"url":[{"@id":"https://link.springer.com/content/pdf/10.1186/s13075-015-0692-4.pdf"},{"@id":"https://link.springer.com/article/10.1186/s13075-015-0692-4/fulltext.html"},{"@id":"http://link.springer.com/content/pdf/10.1186/s13075-015-0692-4"}],"createdAt":"2015-07-27","modifiedAt":"2024-10-14","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360285709230200320","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Pathophysiology of large vessel vasculitis and utility of interleukin-6 inhibition therapy"}]},{"@id":"https://cir.nii.ac.jp/crid/1360857593739416832","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"HLA-B52 allele in giant cell arteritis may indicate diffuse large-vessel vasculitis formation: a retrospective study"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865816812885248","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Human leucocyte antigens and Japanese patients with polymyalgia rheumatica: the protective effect of <i>DRB1*09:01</i>"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1186/s13075-015-0692-4"},{"@type":"CROSSREF","@value":"10.1080/14397595.2018.1546358_references_DOI_K6hANBXrXd6VZhpCq5GRoI5ib1g"},{"@type":"CROSSREF","@value":"10.1186/s13075-021-02618-4_references_DOI_K6hANBXrXd6VZhpCq5GRoI5ib1g"},{"@type":"CROSSREF","@value":"10.1136/rmdopen-2023-003897_references_DOI_K6hANBXrXd6VZhpCq5GRoI5ib1g"}]}