男、女大不同，除了产生性特征差异的性基因染色体外，美国洛杉矶加大最新的研究结果发现，其它器官基因在表达程度上也有极大差异，造成罹患某些特定疾病、对药物效果两性反应不一。
据北美世界日报报道，来自中国的洛杉矶加大(UCLA)医学院心脏病学博士后华裔研究员杨遐(Xia Yang)，耗时近3年，在人类遗传学教授路西斯(Jake Lusis)、病原学教授达克(Thomas Drake)指导以及数名研究员协助下完成研究。
她为了找出人类精神病、糖尿病、肥胖症和心脏病相关的基因线索，采用和人体基因相近度达99%的老鼠作为实验对象，针对脑、肝脏、脂肪和肌肉组织基因深入研究。
该报告发表在8月份《基因体研究》(Genome Research)期刊中。报告第一作者杨遐指出，研究发现男女基因表达上有差异，两者在疾病罹患风险、严重程度及治疗效果上也都有分歧。
研究发现，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积却高于雌性。
杨遐表示，遗传透过DNA传承，经由转录成RNA，然后以蛋白质的形式表现出来，在人体约有三万个基因中，两性间约有一万个基因在转录RNA的过程里所表达出来的量、速度却不一样，对特殊疾病及药物反应也不同。
她说，男女虽然具有同样的基因代码，但研究结果发现，性别调控身体DNA转换成蛋白质的速度，在肝脏、脂肪和肌肉组织里影响了数以千计的基因表现。
杨遐指出，男女在成长过程中，由于性染色体不同而发展出各自的性器官，性器官会产生激素，激素影响基因的呈现，随着年龄的增长，两性间的基因差异会愈来愈扩大。
杨遐表示，过去总认为两性除了性染色体不同外，其它基因都相同，但却不知道性别也会影响基因的呈现。
她强调，目前大部分女性用药剂量都是基于男性临床实验基础上，一旦了解特定疾病有性别上的差异，往后在医学治疗、药物研发上，就可依照性别的不同而研发，增加治愈效果。
杨遐指出，未来将继续研究，解开基因与性别间的奥秘，把心脏疾病、肥胖症相关的基因找出来，创造出治疗方案。
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.
