The influence of ERAP1 gene variants on clinical phenotype in ankylosing spondylitis

• Published in: Scandinavian journal of rheumatology 2016-11, Vol.45 (6), p.474-479
• Main Authors: Nossent, JC, Johnsen, S, Bakland, G
• Format: Article
• Language: English
• Subjects: Adult; Aminopeptidases - genetics; Case-Control Studies; Female; Humans; Interleukin-6 - blood; Male; Middle Aged; Minor Histocompatibility Antigens - genetics; Phenotype; Polymorphism, Single Nucleotide; Spondylitis, Ankylosing - blood; Spondylitis, Ankylosing - genetics; Tumor Necrosis Factor-alpha - blood
• ISSN: 0300-9742; 1502-7732
• DOI: 10.3109/03009742.2016.1150507

Objectives: Endoplasmic reticulum aminopeptidase 1 (ERAP1) gene variants diminish the risk of developing ankylosing spondylitis (AS) through a reduction in ERAP1 activity. We investigated whether disease expression was altered in patients who developed AS despite the presence of two protective ERAP1 variants. Method: We conducted a cross-sectional and longitudinal cohort study of patients with established AS (n = 334, 90% B27+, mean age at study 45 years) for whom clinical data and biological samples were collected during a research visit. Genotyping for the single nucleotide polymorphisms (SNPs) rs27044 and rs30187 was performed on genomic DNA by reverse transcription polymerase chain reaction (RT-PCR) with interleukin (IL)-6 and tumour necrosis factor (TNF) levels determined by a sandwich enzyme-linked immunosorbent assay (ELISA). Associations between genotypes and haplotypes, clinical and serological findings were analysed using SNPstats. Results: Both SNPs were in strong linkage disequilibrium and formed three common haplotypes (C/C 0.65, G/T 0.30, and C/T 0.04). Haplotype C/T carried a lower risk for uveitis [odds ratio (OR) 0.32, p = 0.03] and elevated C-reactive protein (CRP) levels (OR 0.26, p = 0.04). There was no effect of ERAP1 haplotypes on cytokine levels or major outcomes after 8 years of follow-up. Conclusions: The ERAP1 rs27044/rs30187 haplotype C/T is associated with lower risk of extraspinal disease and systemic inflammation in Nordic AS patients but has no impact on IL-6 or TNF levels.