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

Elisa Jaakkola ^1*, Ibi Herzberg ¹, Kari Laiho ², Martin C.N.M. Barnardo ³, Jennifer J. Pointon ¹, Markku Kauppi ², Kalevi Kaarela ⁴, Eva Tuomilehto-Wolf ⁵, Jaakko Tuomilehto ⁶, B. Paul Wordsworth ¹ and Matthew A Brown ¹

¹ Institute of Musculoskeletal Sciences, University of Oxford, United Kingdom
² Rheumatism Foundation Hospital, Finland
³ Oxford Transplant Centre, United Kingdom
⁴ Rheumatism Foundation Hospital, United Kingdom
⁵ National Public Health Institute, Finland
⁶ National Public Health Institute, University of Helsinki, Finland

^* To whom correspondence should be addressed. E-mail: elisa{at}torrekens.org.

Accepted 15 October 2005

Abstract

Objective: To determine the influence of HLA-B27 homozygosity and HLA-DRB1 alleles in the susceptibility to, and severity of, ankylosing spondylitis (AS) in a Finnish population.

Methods: Six hundred and seventy-three individuals from 261 families with AS 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 AS cases. An over-representation of HLA-B27 homozygotes was noted in AS cases (11%) compared with the expected number of HLA-B27 homozygotes under HWE (4%) (OR=3.3, 95% CI=1.6-6.8, p=0.002). HLA-B27 homozygosity was marginally associated with a reduced BASDAI (HLA-B27 homozygotes 4.5±1.6, HLA-B27 heterozygotes 5.4±1.8, 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, 95% CI=1.7-17, p<0.004). HLA-B27 positive cases have a lower average age of symptom onset, 26.7 ± 8 years (mean ± S.D.) compared to HLA-B27 negative cases, 35.7 ± 11.2 years, p<0.0001. No significant associations between HLA-DRB1 alleles and AS susceptibility were noted.

Conclusions: HLA-B27 homozygosity is associated with a moderately increased risk of AS compared with HLA- B27 heterozygosity, but otherwise does not significantly affect clinical manifestations. HLA-B27 positive cases had an earlier age of onset of AS than HLA-B27 negative cases and were more likely to develop AAU. HLA-DRB1 alleles may influence the age of symptom onset of AS, but otherwise do not play a major role in susceptibility to AS.

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

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