Research supported by our BRC has identified a new gene which may explain why so many more women develop lupus than men. Until now, it has been unknown why 90% of people with the condition are female. The advance could lead to new ways to screen for the disease and pick it up sooner. It could also help develop treatments for the condition.
Lupus is an autoimmune condition where the immune system mistakenly attacks the joints, skin and other organs, leading to inflammation. It is thought to affect around 650,000 people in the UK.
The team from King’s College London analysed genetic information and cells collected as part of a number of existing research programmes, including from TwinsUK. Their paper, published in Nature Communications, defines the gene CXorf21 and shows that it may play a role in the condition.
The gene is on the X chromosome, which could explain why more women have the condition, as they have two versions of this chromosome, where men only have one. In women, one of the X chromosomes in every cell is “switched off” so they don’t get double the dose. However, CXorf21 seems to be one of the genes that escapes this process.
The gene also had increased activity when exposed to the immune system molecule interferon, suggesting that it causes a reaction . As lupus is a condition affecting the immune system, these factors made it likely that the gene was involved in the condition.
Professor Tim Vyse, Professor of Molecular Medicine, King’s College London, said: “I am really excited about this work which shows that differences in genetic risk factors between males and females, are important in lupus. We have found a gene for lupus which is more active in women than in men because it is controlled differently in the two sexes. Our work highlights the importance of finding specific treatments for some women with lupus.”
Dr Amy Roberts, Research Fellow at the Department of Twin Research and Genetic Epidemiology at King’s College London, who co-led the research, said: “It is not understood why females are more at risk than males for developing lupus, or indeed most other autoimmune diseases. Historically this has been attributed to hormonal differences.
“However, genes encoded on the X chromosome are good candidates because these are the only chromosomes that are different between the sexes. We examined once such gene, CXorf21, which creates a protein of unknown function. We found that females have more of the CXorf21 protein than males, and this difference is greater still when cells are exposed to inflammatory signals.
“Our study adds support to the hypothesis that sex bias in risk to autoimmune diseases has a genetic basis. More work is now needed to fully understand the function of this protein, which ultimately could lead to both a better understanding of the disease and potential for improved treatments.”