Why do more women develop lupus than men?

15th May 2019 – by Paz Garcia

Photograph of Selena Gomez
Singer and actor Selena Gomez has spoken publicly about living with lupus

King’s College London researchers have identified a new gene which may explain why so many more women develop lupus than men.

Systemic lupus erythematosus – known as SLE or lupus – is an autoimmune condition where the immune system mistakenly attacks the joints, skin and other organs, leading to inflammation.

It’s thought to affect about 65,000 people in the UK. 9 out of every 10 people with the condition are female.

The team included Dr Amy Roberts and Dr Kerrin Small from the Department of Twin Research and Genetic Epidemiology.

The paper was published today in Nature Communications.

Why did they do this research?

Previous research suggests that the X chromosome plays a role in lupus.

Chromosomes are lengths of DNA that contain certain genes on them.

Males have both an X and a Y chromosome, and females have two X chromosomes (XX). Humans only need one dose of the genes on the X chromosome however, so in females one of the X chromosomes in every cell is “switched off” so they don’t get double the dose.

Evidence suggests however that some genes on the switched off X chromosome escape this inactivation.

The team therefore decided to investigate suspect genes on X chromosomes, to see if there were any links with lupus.

What did they find?

The team analysed genetic information and cells collected as part of a number of existing research programmes, including from TwinsUK.

The researchers identified a gene on the X chromosome called CXorf21 as the likely culprit.

They found that the gene was closely linked to another gene known to play a role in lupus which also escapes inactivation in switched off X chromosomes.

The team also found that activity in this gene could be increased in a number of different ways. These included when the gene was not inactivated in switched off X chromosomes and when exposed to immune system molecule interferon – both classic hallmarks of lupus.

What does this mean?

We now have a better understanding of the genetics behind lupus, and why it affects so many more women than men. This could help us develop new screening strategies to pick up new diagnoses sooner, and ultimately help us develop treatments for the condition.

Dr Amy Roberts, who co-led the research, explained:

“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.

Our study supports the idea that males and females have different risks for autoimmune conditions due to genetics. 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.”

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