EXTENDED REPORT

Finnish HLA studies confirm the increased risk conferred by HLA-B27 homozygosity in ankylosing spondylitis

E Jaakkola¹, I Herzberg¹, K Laiho³, M C N M Barnardo², J J Pointon¹, M Kauppi³, K Kaarela³, E Tuomilehto-Wolf⁴, J Tuomilehto⁴, B P Wordsworth¹, M A Brown¹

¹ Botnar Research Centre, Nuffield Orthopaedic Centre, Oxford, United Kingdom
² Transplant Centre, Churchill Hospital, Oxford, United Kingdom
³ Rheumatism Foundation Hospital, Heinola, Finland
⁴ National Public Health Institute, Helsinki, Finland

Correspondence to:
Dr Elisa Jaakkola
Vaasa Central Hospital, Department of Internal Medicine, Hietalahdenkatu 2-4, 65130 Vaasa, Finland; elisa{at}torrekens.org

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.

Abbreviations: 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

Keywords: ankylosing spondylitis; HLA-B27; homozygosity; HLA-DRB1

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