Two distinctive HLA haplotypes harbor the B27 alleles negatively or positively associated with ankylosing spondylitis in Sardinia: implications for disease pathogenesis

Arthritis Rheum. 2003 May;48(5):1385-9. doi: 10.1002/art.10948.


Objective: To compare haplotype distribution in HLA-B27-positive patients with ankylosing spondylitis (AS) and healthy control subjects possessing either AS-associated HLA-B27 alleles or the non-AS-associated HLA-B*2709 allele.

Methods: DNA samples from 47 HLA-B27-positive patients with AS and 76 HLA-B27-positive healthy controls (19 positive and 57 negative for B*2709) living in different areas of Sardinia were collected and typed for HLA class I and class II alleles. The third exon of the B27 gene was analyzed for the presence of Asp(116) or His(116), which differentiates B*2709 from the other two B27 subtypes (B*2705 and B*2702) that are mostly found in Sardinia. The parents of 6 subjects positive for B*2709 were also typed for HLA class I and class II alleles. Statistical analysis was performed by Fisher's exact test.

Results: In Sardinia, the B27 alleles conferring susceptibility to AS appear to be more frequently carried by a haplotype (A2;B27;Cw2;DR16) that reaches its highest frequency in patients with AS (A2 80.8%, B27 100%, Cw2 83%, and DR16 74.5%). Conversely, the non-AS-associated B*2709 allele is more frequently found together with other HLA alleles whose frequencies are inversely correlated with the disease (A32 or A30, Cw1, and DR12). Familial analysis of 6 subjects positive for HLA-B*2709 confirmed the existence of a "Sardinian" haplotype that is not associated with AS (A32;B*2709;Cw1;DR12).

Conclusion: In Sardinia, 2 distinct haplotypes harbor the non-AS-associated HLA-B*2709 allele or the AS-associated B27 alleles. Our findings are compatible with the hypothesis that other genes within the HLA region besides HLA-B27 may play some role in conferring susceptibility to AS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • DNA / blood
  • Female
  • Gene Frequency
  • Genetic Markers
  • Genetic Predisposition to Disease*
  • HLA-B27 Antigen / blood
  • HLA-B27 Antigen / genetics*
  • Haplotypes*
  • Histocompatibility Testing
  • Humans
  • Italy
  • Leukocytes, Mononuclear
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Spondylitis, Ankylosing / genetics*


  • Genetic Markers
  • HLA-B27 Antigen
  • DNA