Santos, Margarida RodriguesCouto, Ana RitaForoni, IrisBettencourt, Bruno FilipeLi, ZhixiuMeneses, RaquelWheeler, LawriePereira, JoaquimPimentel-Santos, FernandoM. Pimentel-Santos, F.Fonseca, João EuricoAlves, HelenaMartinho, AntónioLima, ManuelaBrown, Matthew A.Bruges-Armas, Jácome2018-07-182018-07-182018-06-012044-6055PURE: 5477315PURE UUID: a0b69f49-a1f2-4e2a-930e-a6f86d34a0f0Scopus: 85049483719PubMed: 30018800WOS: 000496144900035http://www.scopus.com/inward/record.url?scp=85049483719&partnerID=8YFLogxKObjectives 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 HLA-B27 AS and HLA-B27 unaffected controls. Methods High-resolution typing of HLA-G, HLA - E and HLA - F 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 HLA-E and HLA-F genes were typed in Australian cohorts. For further confirmation, a group of European-descent patients with AS and unaffected controls were genotyped for Major Histocompatibility Complex SNPs using the Illumina microarray. Results In the Portuguese population, no significant differences were found in HLA-G. For HLA-E, a significant difference was detected for the genotype HLA-E∗01:01:01/01:03:01 (p=0.009; pc=0.009; OR=0.51), with a protection effect. For HLA-F, significant differences were detected in the allele HLA-F∗01:01:02 (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 HLA-F∗01:01:01/01:03:01 (p=0.011; pc=0.043; OR=2.00), suggesting a susceptibility effect. Three G-E-F 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 HLA-E rs1059510 in the Australians and for HLA-F rs1736924 in the European-descent cohorts. Conclusion Our results reveal suggestive AS protective and susceptibility effects from both HLA-E and HLA - F loci, however with population differences. To our knowledge, this is the first study showing association of HLA-F with AS.323281engankylosing spondylitisautoimmune diseasesgene polymorphismHLAinflammationspondyloarthritisRheumatologyImmunology and AllergyImmunologyjournal article10.1136/rmdopen-2018-000677https://www.scopus.com/pages/publications/85049483719