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The Cutting Edge

Same Genes Act Differently in Males and Females; May Explain Gender Gap in Disease, Drug Response

UCLA researchers report that thousands of genes behave differently in the same organs of males and females—
something never detected to this degree. The study, published in
August 2006 in Genome Research, sheds light on why the same
disease often strikes males and females differently, and why the
genders may respond differently to the same drug therapy.

“Our research discovered a genetic disparity that may explain why males and females diverge in terms of disease risk, rate and severity of symptoms,” says Xia Yang, a postdoctoral fellow in cardiology.

The UCLA team scrutinized more than 23,000 genes to measure their expression level in brain, liver, fat and muscle tissue from male and female mice. While each gene functioned the same in both sexes, gender consistently influenced the amount of gene expressed. “We saw striking differences in more than half of the genes’ expression patterns between males and females,” says Dr. Thomas Drake, professor of pathology. “The differences were not related to reproductive systems—they related to the primary functions of a wide variety of organs.”

The gender differences in gene expression also varied by tissue. Affected genes were typically those most involved in the organ’s function, suggesting that gender influences important genes with specialized roles, not the rank-and-file. In the liver, for example, the expression of genes involved in drug metabolism differed by sex. The findings imply that male and female livers function the same, but work at different rates.

“Our findings in the liver may explain why men and women respond differently to the same drug,” says Jake Lusis, professor of human genetics. “One gender may metabolize the drug faster, leaving too little of the medication in the system to produce an effect.”

The findings identify gene targets for potential new therapies, and support the importance of gender-specific clinical trials. Most medication dosages for women have been based on clinical trials conducted primarily on men.
 





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