Sep. 7, 2007 The human genome has now been thoroughly screened in the hunt for the genetic causes of rheumatoid arthritis. The results, which both confirms previous hypotheses and turn the spotlight on entirely new genes, are presented in two articles in the New England Journal of Medicine.
Rheumatoid arthritis is the most common rheumatic disease, and affects approximately one per cent of the population. Its causes are unknown, but scientists believe that the chances of developing the disease are determined as much by genetic factors as they are by environment and lifestyle.
An international team of researchers from Sweden, the USA and Singapore, led by professors Lars Klareskog and Lars Alfredsson at the Swedish medical university Karolinska Institutet together with PhD group leader Mark Seielstad at the A*STAR funded national Genome Institute of Singapore, has compared the genomes of over 1,5000 rheumatics with those of 1,850 controls. Their analysis shows that the DNA of these two groups are at a variance at three sites, two genes previously linked to the disease and a previously unresearched gene complex known as TRAF-C5.
The Swedish and American researchers have also used the same material to examine the significance of a specific area of the genome. They found that yet another gene, STAT 4, could be linked to the disease.
The previously studied genes and the newly discovered TRAF-C5 and STAT4 genes are each important in its own way for the function of the body's immune cells.
"It's exciting that we've found new, single genes that impact on 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," says Professor Klareskog. "Since the two most crucial genes are already known, this shows that we're on the right track."
The studies illustrate the apparent need and growing trend towards conducting genetic research through large-scale international partnerships. Sweden's unique patient register has been of use here for the gathering of samples and for the analysis of the interaction between genetic and environmental factors, while the genetic analysis has been carried out in Singapore using the very latest genomic techniques.
"We're concentrating our efforts onto Singapore as it's a country that is currently investing very actively in bioscience and biotechnology," says Professor Jan Carlstedt-Duke, Dean of Research at Karolinska Institutet. "This is the second study from our partnership with Singapore that's given results."
Publications: TRAF1--C5 as a Risk Locus for Rheumatoid Arthritis; a Genomewide Study, New England Journal of Medicine, 10.1056/nejmoa073491, Online 5 September 2007.
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