title: Finnish HLA studies confirm the increased risk conferred by HLA-B27 homozygosity in ankylosing spondylitis.
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.
authors.affiliation: Botnar Research Centre, Nuffield Orthopaedic Centre, Oxford, United Kingdom. elisa@torrekens.org
authors.forename: E
authors.initials: E
authors.lastname: Jaakkola
authors.forename: I
authors.initials: I
authors.lastname: Herzberg
authors.forename: K
authors.initials: K
authors.lastname: Laiho
authors.forename: M C N M
authors.initials: MC
authors.lastname: Barnardo
authors.forename: J J
authors.initials: JJ
authors.lastname: Pointon
authors.forename: M
authors.initials: M
authors.lastname: Kauppi
authors.forename: K
authors.initials: K
authors.lastname: Kaarela
authors.forename: E
authors.initials: E
authors.lastname: Tuomilehto-Wolf
authors.forename: J
authors.initials: J
authors.lastname: Tuomilehto
authors.forename: B P
authors.initials: BP
authors.lastname: Wordsworth
authors.forename: M A
authors.initials: MA
authors.lastname: Brown
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005387:Finland; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015796:HLA-B27 Antigen / Q000235:genetics* / Q000276:immunology; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006650:Histocompatibility Testing; D006720:Homozygote; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D013167:Spondylitis, Ankylosing / Q000235:genetics* / Q000276:immunology
chemical_list: D015796:HLA-B27 Antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains