Why Women Are 10 Times More Susceptible To Lupus Than Men?

According to a new study, a gene linked to the autoimmune disease lupus, and its location on the X chromosome can explain why females are 10 times more susceptible to the disease than males.

Researchers at UT Southwestern Medical Center identified the gene called IRAK1 as part of an international human genetic study.

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Dr. Chandra Mohan, professor of internal medicine and senior author of the study, said that identifying IRAK1 as a disease gene may also have therapeutic implications.

"Our work also shows that blocking IRAK1 action shuts down lupus in an animal model. Though many genes may be involved in lupus, we only have very limited information on them," he said.

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He also said that locating IRAK1 on the X chromosome also represents a breakthrough in explaining why lupus seems to be sex-linked.

He pointed out that researchers have for long focused on hormonal differences between males and females as a cause of the gender difference.

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"This first demonstration of an X chromosome gene as a disease susceptibility factor in human lupus raises the possibility that the gender difference in rates may in part be attributed to sex chromosome genes," he said.

The study involved 759 people who had developed lupus in their childhood, 5,337 patients who had developed it as adults, and 5,317 healthy controls.

Each group comprised four ethnicities: European-Americans, African-Americans, Asian-Americans and Hispanic-Americans.

Although researchers had found an association between lupus and IRAK1 in previous genetic studies, they failed to find a definite link.

For the current study, the researchers studied five variations of the IRAK1 gene in the subjects, and found that three of the five variants were common in people with either childhood-onset or adult-onset lupus.

For further testing of the link, they took mice of a strain that normally were prone to developing lupus, and engineered them to lack the IRAK1 gene.

It was found that when IRAK1 was absent, the animals lacked symptoms associated with lupus, including kidney malfunction, production of autoimmune antibodies and activation of white blood cells.

"The extensive involvement of IRAK1 in the regulation of the immune response renders its association with lupus a prime candidate for careful genetic and functional analysis," said Mohan.

Future research will investigate the role that X-linked genes, versus hormonal differences, play in the gender susceptibility rates of lupus.

The study appeared online in the Proceedings of the National Academy of Sciences.

Source-ANI
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