Non-classical human leucocyte antigens in ankylosing spondylitis: possible association with HLA-E and HLA-F

ObjectivesAnkylosing 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...

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Published in:Rheumatic & musculoskeletal diseases open 2018-06, Vol.4 (1), p.e000677-e000677
Main Authors: Santos, Margarida Rodrigues, Couto, Ana Rita, Foroni, Iris, Bettencourt, Bruno Filipe, Li, Zhixiu, Meneses, Raquel, Wheeler, Lawrie, Pereira, Joaquim, Pimentel-Santos, Fernando, Fonseca, João Eurico, Alves, Helena, Martinho, António, Lima, Manuela, Brown, Matthew A, Bruges-Armas, Jácome
Format: Article
Language:English
Subjects:
Antigens
Binding sites
Bioinformatics
Design
Disease
Genes
Genomics
Ligands
Peptides
Population
Proteins
Rheumatology
Spondyloarthritis
Studies
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Summary:ObjectivesAnkylosing 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.MethodsHigh-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.ResultsIn 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.ConclusionOur 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.
ISSN:2056-5933
2056-5933
DOI:10.1136/rmdopen-2018-000677