The paternal X chromosome
Studies have shown why women are more likely to have autoimmune diseases
Polina Gershberg, Naked Science
Autoimmune diseases are more common in women than in men. And at times: for example, multiple sclerosis – three times more often, lupus – nine times. In earlier works, the possibility of linking such differences with hormones was considered. The authors of the article published in the Proceedings of the National Academy of Sciences (Golden et al., Parent-of-origin differences in DNA methylation of X chromosome genes in T lymphocytes) suggested that it may be the work of chromosomes. Scientists from the University of California at Los Angeles tested the theory on mice that it is the paternal X chromosome received by girls that is responsible for additional risks of autoimmune diseases.
Autoimmune diseases are an extensive group of disorders. They have different symptoms, and what unites them is that the body's immune system, roughly speaking, begins to attack its host. As a result of such "friendly fire", various pathological conditions, inflammation and destruction of body tissues develop. At least 5-7% of all people suffer from diseases of this group.
As you know, boys get the Y-chromosome from their father, and girls get the X-chromosome. Since girls also receive an X chromosome from their mother, there is a mechanism for deactivating the X chromosome to prevent duplication. DNA methylation blocks the expression of certain genes. Due to this, the vast majority of the genes of the inactive X chromosome "sleep". However, about 15% of the genes can still "bypass" the protection, which is why X genes are more actively expressed in women than in men. In turn, the mechanisms that ensure the functioning of this entire system can negatively affect the overall expression of some traits. Among them are those that ensure the smooth functioning of the immune system. As a result, women may develop a pro-inflammatory response.
The authors of the article in experiments on model animals (mice) found a cluster of five genes associated with the immune system on the X chromosome. It was more pronounced in male mice than in females. After analyzing the difference in the expression of genes associated with the immune system in males and females, the researchers found that the X chromosome, inactivated in females, did not do it randomly. As a rule, it became the X chromosome that was passed down from their fathers.
Earlier studies have shown that additional X-genes give women an advantage: they have a stronger immune response. As you can see, this is not always only a plus.
Further research will be needed to understand to what extent the mouse model is applicable to humans. Despite all the complexity, this may be important, because, according to scientists, the results can lead to the emergence of new approaches to treatment. "If you can find methylation regulators that target these differences, you can reduce immune responses in women to treat autoimmune diseases," says neurologist Rhonda Voskuhl. "In the future, if we consider gender as a biological variable in diseases, this may lead to new therapy strategies."
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