Finnish HLA studies confirm the increased risk conferred by HLA-B27 homozygosity in ankylosing spondylitis. Issue 6 (25th October 2005)

• Record Type: Journal Article
• Authors: Jaakkola, E; Herzberg, I; Laiho, K; Barnardo, M C N M; Pointon, J J; Kauppi, M; Kaarela, K; Tuomilehto-Wolf, E; Tuomilehto, J; Wordsworth, B P; Brown, M A
• Is Part Of: Annals of the rheumatic diseases. Volume 65:Issue 6(2006)
• Page Start: 775
• Page End: 780
• Publication Date: 2005-10-25
• Subjects: AAU, acute anterior uveitis -- BASDAI, Bath ankylosing spondylitis disease activity index -- BASFI, Bath ankylosing spondylitis functional index -- HWE, Hardy–Weinberg equilibrium -- LD, linkage disequilibrium -- MHC, major histocompatibility complex -- QTDT, quantitative transmission disequilibrium test; ankylosing spondylitis -- HLA-B27 -- homozygosity -- HLA-DRB1; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/ard.2005.041103
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Objective: To determine the influence of HLA-B27 homozygosity and HLA-DRB1 alleles in the susceptibility to, and severity of, ankylosing spondylitis in a Finnish population. Methods: 673 individuals from 261 families with ankylosing spondylitis were genotyped for HLA-DRB1 alleles and HLA-B27 heterozygosity/homozygosity. The frequencies of HLA-B27 homozygotes in probands from these families were compared with the expected number of HLA-B27 homozygotes in controls under Hardy–Weinberg equilibrium (HWE). The effect of HLA-DRB1 alleles was assessed using a logistic regression procedure conditioned on HLA-B27 and case–control analysis. Results: HLA-B27 was detected in 93% of cases of ankylosing spondylitis. An overrepresentation of HLA-B27 homozygotes was noted in ankylosing spondylitis (11%) compared with the expected number of HLA-B27 homozygotes under HWE (4%) (odds ratio (OR) = 3.3 (95% confidence interval, 1.6 to 6.8), p = 0.002). HLA-B27 homozygosity was marginally associated with reduced BASDAI ( HLA-B27 homozygotes, 4.5 (1.6); HLA-B27 heterozygotes, 5.4 (1.8) (mean (SD)), p = 0.05). Acute anterior uveitis (AAU) was present in significantly more HLA-B27 positive cases (50%) than HLA-B27 negative cases (16%) (OR = 5.4 (1.7 to 17), p<0.004). HLA-B27 positive cases had a lower average age of symptom onset (26.7 (8.0) years) compared with HLA-B27 negative cases (35.7 (11.2) years) (p<0.0001). Conclusions: HLA-B27 homozygosity is associated with a moderately increased risk of ankylosing spondylitis compared with HLA-B27 heterozygosity. HLA-B27 positive cases had an earlier age of onset of ankylosing spondylitis than HLA-B27 negative cases and were more likely to develop AAU. HLA-DRB1 alleles may influence the age of symptom onset of ankylosing spondylitis.