A Review and Update
Ankylosing spondylitis (AS) is considered a complex genetic disease, as more than one gene is involved. We know the importance and weight the HLA-B27 gene carries in AS, which is currently thought to be responsible for about 30% of the total genetic risk; however, there are numerous other “smaller effect” genes that combined play a much larger role in AS.
Our ongoing challenge in this regard is identifying these remaining genes, which together hold the key to the majority of the genetic puzzle, and with that, to potential new treatments. Each playing a much smaller role in AS than HLA-B27, these smaller effect genes are much more difficult to locate. Genome-wide studies and the establishment of global consortia to share and combine available genetic samples from various locations around the world—thus creating large and robust genetic case samples—are proving effective.
It has been reported that we currently have approximately 20,000 high quality genetic samples worldwide, thanks in large part to:
The discovery in 2007 of a strong association between AS and the ERAP 1 (endoplasmic reticulum associated endopeptidase 1) gene was another big leap in AS research. Not long after this, the ERAP 1 association with AS was shown to be restricted only to cases of HLA-B27 positivity. The discovery of the strong link between HLA-B27 and ERAP 1 in AS marks the first time that any two genes have been found to work in such close synergy in the susceptibility to a complex disease.
We also know of the strong association between AS and related diseases and IL-12, IL-23, as well as the IL-17 gene, the latter having been made abundantly clear by the early success of the IL-17 inhibitor biologic, secukinumab, approved in January 2016.
There are currently more than 60 genes identified as having an association with AS, with the number expected to rise to over 100. The research community has its work cut out for it. We will keep you updated on the latest findings.
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