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

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 , and 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 and 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 . For HLA-E, a significant difference was detected for the genotype (p=0.009; pc=0.009; OR=0.51), with a protection effect. For HLA-F, significant differences were detected in the allele (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 (p=0.011; pc=0.043; OR=2.00), suggesting a susceptibility effect. Three 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 rs1059510 in the Australians and for rs1736924 in the European-descent cohorts.

Conclusion: Our results reveal suggestive AS protective and susceptibility effects from both and loci, however with population differences. To our knowledge, this is the first study showing association of with AS.