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


CONCLUSIONS
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.
Fiorillo
Maria Teresa
MT
University La Sapienza, Rome, Italy.
Cauli
Alberto
A
Carcassi
Carlo
C
Bitti
Pier Paolo
PP
Vacca
Alessandra
A
Passiu
Giuseppe
G
Bettosini
Francesca
F
Mathieu
Alessandro
A
Sorrentino
Rosa
R
D000328:Adult; D004247:DNA / Q000097:blood; D005260:Female; D005787:Gene Frequency; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015796:HLA-B27 Antigen / Q000097:blood / Q000235:genetics*; D006239:Haplotypes; D006650:Histocompatibility Testing; D006801:Humans; D007558:Italy; D007963:Leukocytes, Mononuclear; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D013167:Spondylitis, Ankylosing / Q000235:genetics*
D005819:Genetic Markers; D015796:HLA-B27 Antigen; D004247:DNA