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

E Jaakkola, I Herzberg, K Laiho… - Annals of the …, 2006 - ard.bmj.com
E Jaakkola, I Herzberg, K Laiho, MCNM Barnardo, JJ Pointon, M Kauppi, K Kaarela…
Annals of the rheumatic diseases, 2006ard.bmj.com
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 …
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.
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