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Women's Immune Genes Are Regulated Differently to Men's, Study Finds

FIONA MACDONALD
3 AUG 2015

Researchers have found that there's a big difference between the way that immune system genes are switched off and on in females and the way they're regulated in males, and it seems to be environmental factors, not DNA, that's driving the variation. The discovery could help explain why women are so much more susceptible to autoimmune conditions such as lupus and rheumatoid arthritis than men.

 

Even though our genetic code contains lots of different genes, not all of these are 'active' all the time. "Some genes are virtually always on, like the clock light on a microwave; others sit unused for years at a time, like some regrettable appliance you bought, stuffed into the back of the closet and forgot. Some genes can be always on in one person and always off in another," Jennie Dusheck wrote in a release for Stanford University in the US, where the research was conducted.

The study used a new technique called ATAC-seq, which for the first time ever provides scientists with the ability to study the molecules that regulate all that gene switching on and off. And it revealed that the process varies vastly between individuals - particularly between males and females.

"We were interested in exploring the landscape of gene regulation directly from live people and look at differences," lead researcher Howard Chang told Dusheck. "We asked, 'How different or similar are people?' This is different from asking if they have the same genes."

To work this out, they tested the blood of 12 healthy volunteers, and looked at the expression of 500 genes in immune cells called T cells. They found that 7 percent of the T-cell genes were switched on in different patterns from person to person. And these patterns persisted over time, forming a 'fingerprint' that was unique to each person. 

But even though there were differences between all individuals, "the single greatest predictor for genes’ tendency to turn on and off was the sex of the person," said Chang. "In terms of significance, sex was far more important than all the other things we looked at, perhaps even combined."

They also found that more than a third of the differences in gene expression patterns between individuals couldn't be explained by genetics, suggesting that they're caused by environmental factors such as diet or stress levels instead. This could explain why one twin can have an autoimmune condition, which causes someone's immune system to attack their own cells, while their identical twin can be healthy.

The goal of the study was to use the new technique to find the baseline difference between healthy people's gene expression patterns, so that in future researchers will be able to compare healthy people to those who are unwell.

It's still very early days for this type of research, but in the future, by better understanding how and why certain genes are switched on and off, we could find new treatment pathways for a range of diseases.

Maybe it could also explain why the man flu is so much worse than the regular flu. The results have been published in the journal Cell Systems.