Artigo Acesso aberto Revisado por pares

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

2018; BMJ; Volume: 4; Issue: 1 Linguagem: Inglês

10.1136/rmdopen-2018-000677

ISSN

2056-5933

Autores

Margarida Rodrigues Santos, Ana Rita Couto, I. Foroni, Bruno Filipe Bettencourt, Zhixiu Li, Raquel Meneses, Lawrie Wheeler, Joaquim Polido‐Pereira, Fernando Pimentel-Santos, João Eurico Fonseca, Helena Alves, António Martinho, Manuela Lima, Matthew A. Brown, Jácome Bruges‐Armas,

Tópico(s)

Systemic Lupus Erythematosus Research

Resumo

Objectives 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.

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