男,、女大不同,，除了產(chǎn)生性特征差異的性基因染色體外，美國洛杉磯加大最新的研究結(jié)果發(fā)現(xiàn),，其它器官基因在表達(dá)程度上也有極大差異,，造成罹患某些特定疾病、對(duì)藥物效果兩性反應(yīng)不一,。
據(jù)北美世界日?qǐng)?bào)報(bào)道,，來自中國的洛杉磯加大(UCLA)醫(yī)學(xué)院心臟病學(xué)博士后華裔研究員楊遐(Xia Yang)，耗時(shí)近3年,，在人類遺傳學(xué)教授路西斯(Jake Lusis),、病原學(xué)教授達(dá)克(Thomas Drake)指導(dǎo)以及數(shù)名研究員協(xié)助下完成研究。
她為了找出人類精神病,、糖尿病,、肥胖癥和心臟病相關(guān)的基因線索，采用和人體基因相近度達(dá)99%的老鼠作為實(shí)驗(yàn)對(duì)象,，針對(duì)腦,、肝臟、脂肪和肌肉組織基因深入研究,。
該報(bào)告發(fā)表在8月份《基因體研究》(Genome Research)期刊中,。報(bào)告第一作者楊遐指出，研究發(fā)現(xiàn)男女基因表達(dá)上有差異，兩者在疾病罹患風(fēng)險(xiǎn),、嚴(yán)重程度及治療效果上也都有分歧,。
研究發(fā)現(xiàn)，雌性老鼠罹患肥胖率高于雄性老鼠,，但雄性老鼠腹部脂肪累積卻高于雌性,。
楊遐表示，遺傳透過DNA傳承,，經(jīng)由轉(zhuǎn)錄成RNA,，然后以蛋白質(zhì)的形式表現(xiàn)出來，在人體約有三萬個(gè)基因中,，兩性間約有一萬個(gè)基因在轉(zhuǎn)錄RNA的過程里所表達(dá)出來的量,、速度卻不一樣，對(duì)特殊疾病及藥物反應(yīng)也不同,。
她說,，男女雖然具有同樣的基因代碼，但研究結(jié)果發(fā)現(xiàn),，性別調(diào)控身體DNA轉(zhuǎn)換成蛋白質(zhì)的速度,，在肝臟、脂肪和肌肉組織里影響了數(shù)以千計(jì)的基因表現(xiàn),。
楊遐指出,，男女在成長過程中，由于性染色體不同而發(fā)展出各自的性器官,，性器官會(huì)產(chǎn)生激素,，激素影響基因的呈現(xiàn)，隨著年齡的增長,，兩性間的基因差異會(huì)愈來愈擴(kuò)大,。
楊遐表示，過去總認(rèn)為兩性除了性染色體不同外,，其它基因都相同,，但卻不知道性別也會(huì)影響基因的呈現(xiàn)。
她強(qiáng)調(diào),，目前大部分女性用藥劑量都是基于男性臨床實(shí)驗(yàn)基礎(chǔ)上,，一旦了解特定疾病有性別上的差異，往后在醫(yī)學(xué)治療,、藥物研發(fā)上,，就可依照性別的不同而研發(fā)，增加治愈效果,。
楊遐指出,，未來將繼續(xù)研究，解開基因與性別間的奧秘，把心臟疾病,、肥胖癥相關(guān)的基因找出來,，創(chuàng)造出治療方案。
英文原文：
UCLA Study Finds Same Genes Act Differently in Males and Females; Discovery May Explain Gender Gap in Disease Risk, Drug Response
Scientists may have revealed the origin of the battle of the sexes—in our genes.
UCLA researchers report in a new study that thousands of genes behave differently in the same organs of males and females—something never detected to this degree. The study, published in the August issue of the journal 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.
"We previously had no good understanding of why the sexes vary in their relationship to different diseases," said Xia Yang, Ph.D., first author of the study and postdoctoral fellow in cardiology at the David 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 genomic-research company Rosetta Inpharmatics, the team scrutinized more than 23,000 genes to measure their expression level in male and female tissue.
What they found surprised them. While the function of each gene was 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. Thomas 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 within the same organ, 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," Yang said. "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 the more important genes with specialized roles, not the rank-and-file.
In the liver, for example, the expression of genes involved in drug metabolism differed among men and women. 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," Lusis said. "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," Drake said. "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," Yang said. "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 Heart, Lung, and Blood Institute; 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. Co-authors included Susanna Wang, Leslie Ingram-Drake and Arthur Arnold, all from UCLA, and Eric Schadt of Rosetta Inpharmatics, a subsidiary of Merck & Co., Inc.
