{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T16:32:40Z","timestamp":1759336360927,"version":"3.44.0"},"reference-count":54,"publisher":"BMJ","issue":"1","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["RMD Open"],"accepted":{"date-parts":[[2018,6,10]]},"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Ankylosing spondylitis (AS) is the most prevalent form of spondyloarthritis, with a known genetic association with the HLA-B27 molecule. The aim of this study was to assess the contribution of the HLA-G, HLA-E and HLA-F to AS susceptibility\/protection in Portuguese patients with\u00a0HLA-B27 AS\u00a0and HLA-B27 unaffected controls.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>High-resolution typing of <jats:italic>HLA-G<\/jats:italic>, <jats:italic>HLA<\/jats:italic>\n                     <jats:italic>-<\/jats:italic>\n                     <jats:italic>E<\/jats:italic> and <jats:italic>HLA<\/jats:italic>\n                     <jats:italic>-<\/jats:italic>\n                     <jats:italic>F<\/jats:italic> was performed in 228 patients with HLA-B27 AS and 244 HLA-B27 unaffected controls. Allelic, genotypic and haplotypic frequencies were compared between cohorts. To replicate the results, single nucleotide polymorphisms (SNPs) in <jats:italic>HLA-E<\/jats:italic> and <jats:italic>HLA-F<\/jats:italic> genes were typed in Australian cohorts. For further confirmation, a group of European-descent patients with\u00a0AS and unaffected controls were genotyped for Major Histocompatibility Complex SNPs using the Illumina microarray.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In the Portuguese population, no significant differences were found in <jats:italic>HLA-G<\/jats:italic>. For HLA-E, a significant difference was detected for the genotype <jats:italic>HLA-E*01:01:01\/01:03:01<\/jats:italic> (p=0.009; pc=0.009; OR=0.51), with a protection effect. For HLA-F, significant differences were detected in the allele <jats:italic>HLA-F*01:01:02<\/jats:italic> (p=0.0049; pc=0.0098; OR=0.60) and corresponding SNP rs2075682 (p=0.0004; pc=0.0008; OR=0.53), suggesting protection and in the genotype <jats:italic>HLA-F*01:01:01\/01:03:01<\/jats:italic> (p=0.011; pc=0.043; OR=2.00), suggesting a susceptibility effect. Three <jats:italic>G-E-F<\/jats:italic> haplotypes with significant differences were detected but occur in a very small number of individuals. The only significant differences detected in the replication studies were for <jats:italic>HLA-E<\/jats:italic> rs1059510 in the Australians and for <jats:italic>HLA-F<\/jats:italic> rs1736924 in the European-descent cohorts.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our results reveal suggestive AS protective and susceptibility effects from both <jats:italic>HLA-E<\/jats:italic> and <jats:italic>HLA<\/jats:italic>\n                     <jats:italic>-<\/jats:italic>\n                     <jats:italic>F <\/jats:italic>loci, however with population differences. To our knowledge, this is the first study showing association of <jats:italic>HLA-F<\/jats:italic> with AS.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/rmdopen-2018-000677","type":"journal-article","created":{"date-parts":[[2018,6,28]],"date-time":"2018-06-28T10:16:13Z","timestamp":1530180973000},"page":"e000677","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Non-classical human leucocyte antigens in ankylosing spondylitis:\u00a0possible association with HLA-E and HLA-F"],"prefix":"10.1136","volume":"4","author":[{"given":"Margarida Rodrigues","family":"Santos","sequence":"first","affiliation":[{"name":"Servi\u00e7o Especializado de Epidemiologia e Biologia Molecular, Hospital de Santo Espirito da Ilha Terceira,\u00a0EPER, Angra do Heroismo, Portugal"}]},{"given":"Ana Rita","family":"Couto","sequence":"additional","affiliation":[{"name":"Servi\u00e7o Especializado de Epidemiologia e Biologia Molecular, Hospital de Santo Espirito da Ilha Terceira,\u00a0EPER, Angra do Heroismo, Portugal"}]},{"given":"Iris","family":"Foroni","sequence":"additional","affiliation":[{"name":"Servi\u00e7o Especializado de Epidemiologia e Biologia Molecular, Hospital de Santo Espirito da Ilha Terceira,\u00a0EPER, Angra do Heroismo, Portugal"}]},{"given":"Bruno Filipe","family":"Bettencourt","sequence":"additional","affiliation":[{"name":"Servi\u00e7o Especializado de Epidemiologia e Biologia Molecular, Hospital de Santo Espirito da Ilha Terceira,\u00a0EPER, Angra do Heroismo, Portugal"}]},{"given":"Zhixiu","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Health and Biomedical Innovation, Translational Research Institute, Queensland University of Technology, Brisbane, Australia"}]},{"given":"Raquel","family":"Meneses","sequence":"additional","affiliation":[{"name":"Servi\u00e7o Especializado de Epidemiologia e Biologia Molecular, Hospital de Santo Espirito da Ilha Terceira,\u00a0EPER, Angra do Heroismo, Portugal"}]},{"given":"Lawrie","family":"Wheeler","sequence":"additional","affiliation":[{"name":"Institute of Health and Biomedical Innovation, Translational Research Institute, Queensland University of Technology, Brisbane, Australia"}]},{"given":"Joaquim","family":"Pereira","sequence":"additional","affiliation":[{"name":"Servi\u00e7o Especializado de Epidemiologia e Biologia Molecular, Hospital de Santo Espirito da Ilha Terceira,\u00a0EPER, Angra do Heroismo, Portugal"}]},{"given":"Fernando","family":"Pimentel-Santos","sequence":"additional","affiliation":[{"name":"CEDOC, Faculdade de Ci\u00eancias M\u00e9dicas, Universidade Nova de Lisboa, Lisboa, Portugal"}]},{"given":"Jo\u00e3o Eurico","family":"Fonseca","sequence":"additional","affiliation":[{"name":"IMM, Universidade de Lisboa, Lisboa, Portugal"}]},{"given":"Helena","family":"Alves","sequence":"additional","affiliation":[{"name":"Centro de Histocompatibilidade do Norte, Instituto Portugu\u00eas do Sangue e da Transplanta\u00e7\u00e3o, Porto, Portugal"}]},{"given":"Ant\u00f3nio","family":"Martinho","sequence":"additional","affiliation":[{"name":"Centro de Sangue e Transplanta\u00e7\u00e3o de Coimbra, Instituto Portugu\u00eas do Sangue e da Transplanta\u00e7\u00e3o, Coimbra, Portugal"}]},{"given":"Manuela","family":"Lima","sequence":"additional","affiliation":[{"name":"Faculdade de Ci\u00eancias e Tecnologia, Universidade dos A\u00e7ores, Ponta Delgada, Portugal"}]},{"given":"Matthew A","family":"Brown","sequence":"additional","affiliation":[{"name":"Institute of Health and Biomedical Innovation, Translational Research Institute, Queensland University of Technology, Brisbane, Australia"}]},{"given":"J\u00e1come","family":"Bruges-Armas","sequence":"additional","affiliation":[{"name":"Servi\u00e7o Especializado de Epidemiologia e Biologia Molecular, Hospital de Santo Espirito da Ilha Terceira,\u00a0EPER, Angra do Heroismo, Portugal"},{"name":"CEDOC, Faculdade de 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