Journal
ARTHRITIS AND RHEUMATISM
Volume 48, Issue 5, Pages 1385-1389Publisher
WILEY
DOI: 10.1002/art.10948
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Objective. To compare haplotype distribution in HILA-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 11 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 11 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 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.
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