IRAK1’s X-chromosome location may explain why females are more susceptible, according to PNAS article.
Researchers at UT Southwestern Medical Center have confirmed a link between the IRAK1 gene and the autoimmune disease lupus. Since it is located on the X chromosome, the team suggests that it helps explain why females are 10 times more susceptible to the disease than males.
“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,” says Chandra Mohan, M.D., Ph.D., senior author of the study. Past research has mainly focused on hormonal differences between males and females, according to Dr. Mohan.
The multicenter study, which appears this week online in Proceedings of the National Academy of Sciences, involved 759 people who developed lupus as children, 5,337 patients who developed it as adults, and 5,317 healthy controls. Each group comprised four ethnicities: European-Americans, African-Americans, Asian-Americans, and Hispanic-Americans.
To validate the previously identified association between lupus and IRAK1, a gene involved in immune response, the researchers studied five variations of the IRAK1 gene in the subjects. They found that three of the five variants were common in people with either childhood-onset or adult-onset lupus.
The researchers then took mice of a strain that normally is prone to developing lupus and engineered them to lack the IRAK1 gene. In the absence of IRAK1, the animals did not develop symptoms associated with lupus, including kidney malfunction, production of autoimmune antibodies, and activation of white blood cells.
Future research will investigate the role that X-linked genes versus hormonal differences play in the gender susceptibility rates of lupus.