More genetic links to RA

Two studies published in the New England Journal of Medicine have confirmed previous genetic links to rheumatoid arthritis and pinpoint two others as suspect.

An international team of researchers from Sweden, the USA and Singapore, led by professors Lars Klareskog and Lars Alfredsson at the Karolinska Institutet and group leader Mark Seielstad at the Genome Institute of Singapore, has compared the genomes of over 15000 rheumatics with those of 1850 controls.

Their analysis shows that there is a variance at three sites, two genes previously linked to the disease and a new one, TRAF-C5.

The Swedish and American researchers have also used the same material to examine the significance of a specific area of the genome and found that yet another gene, STAT 4, could be linked to the disease.

The two previously known associations for rheumatoid are alleles of the HLA-DRB1 gene and PTPN22. A recent Wellcome Trust Case Control Consortium study led by the University of Manchester also found links with the IL2 receptor, which is thought to have an important role in preventing autoimmunity.

The TRAF-C5 and STAT4 genes are also important in their own way for the function of the body's immune cells, the Swedish researchers said.

"It's exciting that we've found new, single genes that [affect] the risk of disease, but what's most important is that we've now got a broader base for understanding the mechanisms behind the development and course of the disease," Klareskog said. "Since the two most crucial genes are already known, this shows that we're on the right track."

The STAT4 association was made by a team led by Dr Peter Gregersen, head of the Center for Genomics & Human Genetics at New York's Feinstein Institute.

This research found that having this variant of STAT4 conferred a 30 per cent increased risk for developing rheumatoid arthritis. There was also a strong correlation with lupus, another autoimmune disease.