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

Abstract

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.

• Authors: Maria Teresa Fiorillo, Alberto Cauli, Carlo Carcassi, Pier Paolo Bitti, Alessandra Vacca, Giuseppe Passiu, Francesca Bettosini, Alessandro Mathieu, Rosa Sorrentino
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 48 Issue 5 Pg. 1385-9 (May 2003) ISSN: 0004-3591 [Print] United States
• PMID: 12746911 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Genetic Markers
• HLA-B27 Antigen
• DNA

Topics

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