British scientists have identified 14 new genes that can lead to rheumatoid arthritis – including some that are linked to the female X-chromosome. The groundbreaking discovery helps explain why women are more likely to get the disease and could lead to more effective treatments.
Rheumatoid arthritis (RA) is a long-term autoimmune disease that causes inflammation of the joints and surrounding tissue. It affects an estimated 2 million people in the United States and about one percent of the world’s population. Women are three times more likely than men to get RA.
The discovery of the 14 genes by scientists at the Arthritis Research UK Epidemiology Unit at the University of Manchester adds to the 32 other genes they have already been identified. Researchers believe they have now uncovered the vast majority of disease-causing genes for RA.
“This work will have a great impact on the clinical treatment of arthritis,” predicted Dr. Stephen Eyre, who co-authored a study published in the journal Nature Genetics. “We have already found three genes that are targets for drugs, leaving a further 43 genes with the potential for drug development, helping the third of patients who fail to respond well to current medications.”
By studying DNA samples from 27,000 RA patients from around the world, the UK researchers are the first to establish a genetic association between rheumatoid arthritis and the X chromosome.
“Although patients who first present at clinic have similar symptoms, it is likely that their route to developing disease has involved a varied path,” said Dr. Eyre. “The genetic findings can help divide patients into smaller groups with more similar types of rheumatoid arthritis and assist in the allocation of therapies and disease management.”
Lifestyle and environmental factors, such as smoking, diet, pregnancy and infection are thought to play a role in RA, but it is now believed that a person’s genetic makeup influences their susceptibility to the condition. It is those genetic clues that researchers say make this study so valuable.
“We observed remarkable similarities with genetic markers associated with other autoimmune diseases,” said lead author Jane Worthington. ”As a result of our findings, we now know that genetic variations at over 45 regions of the genome determine susceptibility to this form of arthritis.”
“Our future work will focus on understanding how the simple genetic changes alter normal biological processes and lead to disease. Ultimately, this will help us to develop novel therapies and improved targeting of existing drugs.”
The medical director of Arthritis Research UK said the sheer size of the study has added a significant amount to the current knowledge of the genetic basis of rheumatoid arthritis.
“We hope that this research will lead to a greater understanding of the disease,” said Professor Alan Silman, “and allow us to develop targeted drug treatments for the millions of people currently living with rheumatoid arthritis.”