Rheumatoid arthritis (RA) is a common and painful autoimmune disease, marked by inflammation of the lining of the joints and damaged bone and cartilage. A new study by Ryo Yamada and colleagues to appear in the August issue of Nature Genetics identifies a gene variant that confers susceptibility to the disease.
Yamada and colleagues followed up on previous studies that had identified a region on chromosome 1 as being linked to susceptibility to RA. They narrowed down the region to a gene called PADI4, which encodes the enzyme peptidylarginine deiminase 4, a member of a group of proteins whose function is to convert the amino acid arginine to citrulline. It was already known that individuals with RA often have antibodies against their own ‘citrullinated’ proteins, and that these antibodies appear very early on in the disease progression. Yamada and coworkers showed that the particular PADI4 variant that was associated with susceptibility to RA may allow for the production of more of the PADI4 protein. This would presumably result in increased citrullination, and indeed, they found that individuals with two copies of the susceptibility variant were more likely to test positive for the presence of antibodies to citrullinated proteins.
So far, the only genes linked to RA susceptibility have been the HLA genes, which account for about half of the genetic contribution to RA risk. The authors indicate that about 17% of all individuals with RA, at least in the Japanese population under study, can attribute their disease to variation in PADI4, suggesting that it is a significant risk factor.
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(C) Nature Genetics press release.
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