Non-major-histocompatibility-complex genetics of ankylosing spondylitis.
There is strong evidence from twin and family studies indicating that a substantial proportion of the heritability of susceptibility to ankylosing spondylitis (AS) and its clinical manifestations is encoded by non-major-histocompatibility-complex genes. Efforts to identify these genes have included genomewide linkage studies and candidate gene association studies. One region, the interleukin (IL)-1 gene complex on chromosome 2, has been repeatedly associated with AS in both Caucasians and Asians. It is likely that more than one gene in this complex is involved in AS, with the strongest evidence to date implicating IL-1A. Identifying the genes underlying other linkage regions has been difficult due to the lack of obvious candidates and the low power of most studies to date to identify genes of the small to moderate magnitude that are likely to be involved. The field is moving towards genomewide association analysis, involving much larger datasets of unrelated cases and controls. Early successes using this approach in other diseases indicates that it is likely to identify genes in common diseases like AS, but there remains the risk that the common-variant, common-disease hypothesis will not hold true in AS. Nonetheless, it is appropriate for the field to be cautiously optimistic that the next few years will bring great advances in our understanding of the genetics of this condition.
Brown
Matthew A
MA
Centre for Immunology and Cancer Research, Princess Alexandra Hospital, Ipswich Road, Woolloongabba, QLD 4102, Australia. mbrown@cicr.uq.edu.au
D044466:Asian People / Q000208:ethnology; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D005192:Family Health; D008040:Genetic Linkage; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D015796:HLA-B27 Antigen / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D008285:Major Histocompatibility Complex; D053473:Nod2 Signaling Adaptor Protein; D028061:Phosphate Transport Proteins / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D013167:Spondylitis, Ankylosing / Q000208:ethnology / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics; D018433:Twin Studies as Topic; D044465:White People / Q000208:ethnology
C498770:ANKH protein, human; D005819:Genetic Markers; D015796:HLA-B27 Antigen; D007375:Interleukin-1; D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D028061:Phosphate Transport Proteins; D011506:Proteins; D016212:Transforming Growth Factor beta; D019389:Cytochrome P-450 CYP2D6