The association of
HLA-B27 with
ankylosing spondylitis (AS) is the strongest among all
inflammatory diseases. However, the exact role of these molecules in disease
pathogenesis is still unknown. The existence of
HLA-B27 variants rarely found in patients introduces a further level of complexity. It is now accepted that other genes of minor impact contribute to modify disease susceptibility and these genes might be diverse in different populations depending on the
genetic background. We report here a study performed in Sardinia, an
outlier population in which two major
HLA-B27 subtypes are present, B (*)2705 strongly associated with AS and B (*)2709 which is not, and show the co-occurrence of the B (*)2705
allele with a
single nucleotide polymorphism (
SNP) mapping at 3'-UTR of the receptor 1 (
VIPR1) for the
vasoactive intestinal peptide (VIP), a
neuropeptide with
anti-inflammatory properties. This same
SNP is associated with a different kinetics of down-modulation of the
VIPR1 mRNA in
monocytes after exposure to
lipopolysaccharide (P=0.004). This particular setting,
HLA-B (*)2705 and a functional polymorphism in
VIPR1 gene, might be due to a
founder effect or might be the result of a
selective pressure. Irrespectively, the consequent downregulation of this receptor in the presence of a 'danger' signal might influence susceptibility to AS.Genes and Immunity (2008) 9, 659-667; doi:10.1038/gene.2008.60; published online 31 July 2008.
