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Jul. 8--An individual's sex determines activity of many more genes than previously thought, which may play a major role in how diseases affect men and women differently, according to a surprising study.
Drs. Jake Lusis and Thomas Drake of UCLA's David Geffen School of Medicine in Los Angeles and colleagues at Merck Inc. discovered that gender influences genes that are working differently in males and females and plays a role in an individual's risk for illness, and response to medications.
"We saw striking differences in more than half of the genes' expression patterns between males and females," Drake said. "We didn't expect that." He said no one has shown this genetic gender gap at such levels.
In the study, in the August issue of the journal Genome Research, the scientists studied genetic activity variations related to diabetes, obesity and cardiovascular diseases. The research was conducted in mice, but Drake said mice and humans share 99 percent of their genes.
"Sex may play a much bigger role in disease than anyone ever expected," Drake added. "The fact that we do see sex-related differences suggests that we need to pay more attention to this," he added. "The differences are very striking."
Scientists have long known that men are at higher risk for certain diseases, and women for others. This new finding might explain why: Genes are working the same way in men and women, but if the genes are activated at a higher level there will be different effects on tissues, and risk will differ.
The female sex genes are on the X-chromosome; the male, on the Y-chromosome. The scientists took tissue from several organs, including the liver, heart and brain, and analyzed what genes were working in the specific tissues and whether there were differences based on gender alone.
There were. The researchers found sex influenced activity of the majority of genes in the tissues studied, except the brain.
Xia Yang, first author on the paper and a postdoctoral fellow in cardiology at UCLA, said the study suggests "gender influences how disease develops." It also seems to regulate response to medicines. For instance, Drake said, the liver in men and women receives different genetic signals that work to metabolize drugs. This can influence dosage and side effects.
Thirty thousand genes make up the human genome. The study looked at 23,000 of those and how their behavior was affected by sex genes. The genes on the sex chromosomes account for fewer than 2 percent of the total number of human genes. Despite this, more than half of genes studied behaved differently based on gender.
"The wind is now blowing in another direction," said Arthur P. Arnold, a professor and chairman of physiological science at UCLA. "On a genetic level, there are more sex differences than we thought. It's changed my view [of disease susceptibility] a lot."
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Copyright (c) 2006, Newsday, Melville, N.Y.
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