Ankylosing Spondylitis Ankylosing spondylitis is an autoimmune condition that is apparently found in about 200 men and one in 500 women in the U.K. A study put forth by a collaborated effort of the Australo-Anglo-American Spondyloarthritis Consortium and the Wellcome Trust Case Control Consortium scientists has revealed a cascade of genetic factors linked with the increased risk of the disease and cues to develop efficient therapies thereon.

The study affirms the gene-gene communication apparently observed in humans. This analysis examined the genomes of 3,023 cases and compared it with 8,779 healthy controls. A sequence of genetic areas came to fore that could be implied with the disorder. The findings were affirmed in a separate set of 2111 cases and 4483 controls.

Professor Peter Donnelly from the University of Oxford, Chair of the Wellcome Trust Case Control Consortium, commented, “Thanks to over 5000 people with ankylosing spondylitis who have provided DNA samples, we were able to undertake the largest study of the genetics of this painful and often disabling disease. It revealed important, and in some cases surprising, new insights into the disease.”

The investigation unfolded three portions of the genome namely the RUNX3, LTBR and TNFRSF1A. The genetic variants in these were seemingly related to ankylosing spondylitis. They also found 4 additional genomes that may result in the aforesaid condition namely the PTGER4, TBKBP1, ANTXR2 and CARD9.

Another aspect observed was that of the specific procedure in signals that are transited among cells called the IL-23R pathway which supposedly could be a potential drug target. Yet, scientists couldn’t figure out the link between HLA-B27 and the condition. Hence, certain clues regarding the same were unraveled. However, investigators have always known that this variant is increasingly present in 9 out of 10 patients with ankylosing spondylitis. Even though not everyone with this type develops this condition, those who possess it apparently stand an 80% increased risk than those who do not carry the gene.

In spite of this knowledge, the main mechanism of the genome’s working remains undiscovered. The scientists found that the gene ERAP1 may communicate with HLA-B27 and influence disease risk. For persons who carry HLA-B27, the risk of contracting the disorder supposedly decrease by factor of 4 if they carry 2 copies of ERAP 1 that act as the shielding variants.

ERAP1 shows this effect by breaking down proteins in the body into smaller molecules called peptides. The interaction between this gene and HLA-B27 reflects a different way these peptides are shown to the immune system. This process is crucial for accelerating an immune responsiveness to intruding pathogens. If this procedure goes haywire, then it may result in the in inflammation and damage to the immune system.

The study revealed that certain variants of ERAP1 guard against the development of ankylosing spondylitis by decreasing the proportion of peptide available to HLA-B27 within cells. According to analysts inhibition of ERAP1 may help improve the disorder.

Furthermore, they also analyzed the genetic make-up of persons who were suffering from ankylosing spondylitis but did not carry the HLA-B27 variant. A number of genetic link-ups came to fore. These findings pave way to a better understanding of the similarities involved in the HLA-B27 positive and negative ankylosing spondylitis development mechanisms.

The study is published in the journal ‘Nature Genetics’.