Same Genes Act Differently In Males And Females; Discovery May Explain Gender Ga

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Same Genes Act Differently In Males And Females; Discovery May

Explain Gender Gap In Disease Risk, Drug Response - UCLA Study Finds

http://www.medicalnewstoday.com/medicalnews.php?newsid=46763

UCLA researchers report that thousands of genes behave differently in

the same organs of males and females - something never detected to

this degree. Published in the August issue of Genome Research, the

study sheds light on why the same disease often strikes males and

females differently, and why the genders may respond differently to

the same drug.

" We previously had no good understanding of why the sexes vary in

their relationship to different diseases, " explained Xia Yang, Ph.D.,

first author and postdoctoral fellow in cardiology at the

Geffen School of Medicine at UCLA. " Our study discovered a genetic

disparity that may explain why males and females diverge in terms of

disease risk, rate and severity. "

" This research holds important implications for understanding

disorders such as diabetes, heart disease and obesity, and identifies

targets for the development of gender-specific therapies, " said Jake

Lusis, Ph.D., co-investigator and UCLA professor of human genetics.

The UCLA team examined brain, liver, fat and muscle tissue from mice

with the goal of finding genetic clues related to mental illnesses,

diabetes, obesity and atherosclerosis. Humans and mice share 99

percent of their genes.

The scientists focused on gene expression -- the process by which a

gene's DNA sequence is converted into cellular proteins. With the

help of Rosetta Informatics, the team scrutinized more than 23,000

genes to measure their expression level in male and female tissue.

What they found surprised them. While each gene functioned the same

in both sexes, the scientists found a direct correlation between

gender and the amount of gene expressed.

" We saw striking and measurable differences in more than half of the

genes' expression patterns between males and females, " said Dr.

Drake, co-investigator and UCLA professor of pathology. " We

didn't expect that. No one has previously demonstrated this genetic

gender gap at such high levels. "

UCLA is the first to uncover a gender difference in gene expression

in fat and muscle tissue. Earlier studies have identified roughly

1,000 sex-biased genes in the liver, and other research has found a

combined total of 60 gender-influenced genes in the brain - about one-

tenth of what the UCLA team discovered in these organs.

Even in the same organ, the researchers identified scores of genes

that varied in expression levels between the sexes. Gender

consistently influenced the expression levels of thousands of genes

in the liver, fat and muscle tissue. This effect was slightly more

limited in the brain, where hundreds, not thousands, of genes showed

different expression patterns.

" Males and females share the same genetic code, but our findings

imply that gender regulates how quickly the body can convert DNA to

proteins, " said Yang. " This suggests that gender influences how

disease develops. "

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, " noted Lusis. " Studies show that

aspirin is more effective at preventing heart attack in men than

women. One gender may metabolize the drug faster, leaving too little

of the medication in the system to produce an effect. "

" At the genetic level, the only difference between the genders is the

sex chromosomes, " said Drake. " Out of the more than 30,000 genes that

make up the human genome, the X and Y chromosomes account for less

than 2 percent of the body's genes. But when we looked at the gene

expression in these four tissues, more than half of the genes

differed significantly between the sexes. The differences were not

related to reproductive systems - they were visible across the board

and related to primary functions of a wide variety of organs. "

The UCLA findings support the importance of gender-specific clinical

trials. Most medication dosages for women have been based on clinical

trials primarily conducted on men.

" This research represents a significant step forward in deepening our

understanding of gender-based differences in medicine, " said Dr.

Janet Pregler, director of the Iris Cantor-UCLA Women's Health

Center. The center's executive advisory board, a group of

businesswomen interested in advancing women's health, helped fund the

study.

" Many of the genes we identified relate to processes that influence

common diseases, " said Yang. " This is crucial, because once we

understand the gender gap in these disease mechanisms, we can create

new strategies for designing and testing new sex-specific drugs. "

The National Institute for Heart, Lung and Blood; the National

Institute of Diabetes and Digestive and Kidney Diseases; and the UCLA

National Center for Excellence in Women's Health also supported the

study. Coauthors included na Wang, Ingram-Drake and

Arthur Arnold, all from UCLA, and Schadt of Rosetta

Inpharmatics, a subsidiary of Merck and Co.

http://www.cshl.edu