据physorg网站2006年7月25日报道，双胞胎同吃同睡，很多都无法把他们区分开来。一模一样的双胞胎一同成长，他们分享着几乎同样的东西，包括他们的基因。但是，有些时候当从遗传学上来预测，他们俩人都应当有健康问题的时候往往只一位会面临健康问题。
美国密歇根大学医学院科学家们正着手对有着惊人相似的双胞胎为何在面临一些像风湿性关节炎之类的疾病时有如此大的差异展开研究。
美国密歇根大学医学院研究人员在风湿性关节炎或者风湿病中发现了三种过量表达基因，研究人员先前并不知道这三种基因与这些疾病有关。他们同时还发现非基因因素也影响着这三种基因的表现。双胞胎体内这三种基因表现形势的差异导致双胞胎中只有一个会得风湿病。美国密歇根大学医学院研究人员的研究论文刊登在《关节炎和风湿病》期刊的7月版中。
风湿病是一种慢性炎症性疾病，它会对关节造成损害。风湿病会引发疼痛、令人丧失行动能力和导致骨骼畸形。210万美国人正忍受着风湿病的折磨。有很多遗传因素会令人们存在患风湿病的高风险性。只有约15%的双胞胎能够同时避免风湿病。
科学家对11对单卵双胞胎的基因表现方式进行了对比，这些双胞胎共享着同一个卵子，具有同样的遗传。他们中只有一个患有风湿病。他们发现这三种基因在患有风湿病的双胞胎体内的量远远高于没有患风湿病的双胞胎。这是首次有关在单卵双胞胎中检测基因表现方式来研究风湿病的报道。
该研究的参与者之一，美国密歇根大学医学院内科助理教授约瑟夫?胡洛西特兹医学博士说，“我们正在努力解答风湿病中的一种关键问题，即两个具有同样基因的患者为什么会得不同的疾病。一模一样的双胞胎为我们提供了解答此项问题的最佳途径。”双胞胎研究的优势在于他们具有严格相同的基因信息。因此，基因表现的差异性就完全应当归功于不同的环境因素，而不是遗传。这些环境因素引发一个随机基因突变或者影响脱氧核糖核酸的打包方式。
胡洛西特兹说，“这令患有严格相同疾病、具有严格相同症状和反应的病人在接受治疗时存在很大的可变性。由环境因素引发的基因表现方式的差异性会对脱氧核糖核酸进行修改，从而引发出大量可变性。”
科学家将蛋白质中最显著的三种过量基因代码称之为laeverin。laeverin是一种酶，它可以破坏某种蛋白质类型。科学家们猜测laeverin是通过使软骨和骨骼退化来加重风湿病对关节组织损伤的。另一种以前没有确认的蛋白质基因代码11β-HSD2，11β-HSD2可以帮助抑制考的索激素。考的索激素可以对压力做出反应，同时还具备抵抗炎症影响的能力。该研究发现11β-HSD2在风湿病患者体内过量能对风湿病患者的共有特征作出解释。胡洛西特兹说，“很久以前我们就知道风湿病患者体内缺乏考的索。”
美国密歇根大学医学院科学家研究发现的第三种基因代码为Cyr61，Cyr61在血管新生过程中扮演着角色，血管新生是指一个区域新血管重生的过程。
在风湿病初期阶段，关节组织开始生长和分裂成一个类似于良性肿瘤的瘤。这个不断生长的块分泌使组织退化的蛋白质，并利用血管新生来恢复新的血管为这个瘤提供营养。血管新生过程中的Cyr61可能也与这个过程有关。
胡洛西特兹说，“我们进行的这项研究只是对该方法可能揭示出来的东西进行了初步研究。在双胞胎体内还存在大量表现存在差异的基因。我们仅仅开始着手对风湿病是如何以不同的方式影响人类展开研究。我们所新发现的基因对了解疾病的本性，推动风湿病新治疗策略的制定非常重要。”
此项研究得到了美国国家卫生研究院、关节炎基金会、研究和发展办公室和退伍军人事务部的资助。
此项研究的主要研究人员为美国密歇根大学医学院内科系研究员克里斯蒂安?S?哈阿斯医学博士和美国密歇根大学医学院病理学系助理研究员查德?J?克瑞通。辅助研究人员为美国密歇根大学医学院风湿病系研究员徐军霹医学博士和物理学博士、病理学系副研究员艾拉?马因里博士、风湿病学和内科教授艾丽萨?E?科赫医学博士、内科系研究调查员宋宁博士、病理学和泌尿学助理教授阿鲁尔?M?切奈阳医学博士和物理学博士和西北大学医学院肯尼恩?海因斯医学博士。
英文原文：
How can identical twins be genetically different?
They sleep together, eat together, and most people find it impossible to tell them apart. Identical twins who grow up together share just about everything, including their genes. But sometimes only one twin will have health problems when genetics predicts both of them should.
Scientists at the University of Michigan Medical School are just beginning to understand how two people who are so similar biologically can be so different when it comes to the development of diseases like rheumatoid arthritis.
U-M researchers have discovered three genes that are over-expressed in rheumatoid arthritis, or RA, that were not known to be associated with the disease before. They also found that non-genetic factors influenced the expression of these genes and that the expression patterns varied between identical twins where only one twin had RA. Results of the U-M study were published in the July issue of Arthritis and Rheumatism.
RA is a chronic inflammatory disease that damages joints. RA causes pain, loss of movement, and bone deformities. It affects 2.1 million Americans. There are many genetic factors that put people at a high-risk for developing RA, yet only 15 percent of identical twins will both develop it.
Scientists compared gene expression patterns of 11 pairs of monozygotic twins, who shared the same egg and were genetically identical, but only one of them had RA. They found three new genes that were significantly over-expressed in the twin with RA compared to the one without the disease. This is the first report for RA that examines gene expression patterns in monozygotic twins.
“This is the crux of the issue we are trying to address in RA -- how two patients can have the same genes but different disease outcomes. Identical twins represent the best experimental system to address this question,” says Joseph Holoshitz, M.D., an associate professor of internal medicine at U-M Medical School and co-author of the study.
The advantage of studying twins is that they start out with the exact same genetic information. Therefore, differences in gene expression are attributable to different environmental factors rather than genetics. Such factors could cause a random genetic mutation or affects how DNA is packaged.
“There’s a lot of variability in the severity of the disease, symptoms, and the response a patient will have to treatment. Differences in the expression of genes caused by environmental factors that modify DNA have a lot to do with this variability,” says Holoshitz.
The most significantly over-expressed of the three genes codes for a protein called laeverin. This is an enzyme that destroys certain types of proteins. Scientists hypothesize that laeverin promotes the tissue damage of the joint found in RA by degrading cartilage and bone.
Another previously unidentified gene codes for a protein called 11β-HSD2 that helps deactivate the hormone cortisol. This hormone is involved in the response to stress and also has anti-inflammatory effects. The discovery that 11β-HSD2 is over-expressed in patients may explain a common characteristic of RA patients.
“It has been known for a long time that there is a deficiency of cortisol in RA patients,” says Holoshitz.
The third gene U-M scientists discovered codes for Cyr61, which plays a role in angiogenesis, a process that recruits new blood vessels to an area.
In the early stages of RA, the tissue in the joint begins to grow and divide similarly to a benign tumor. The growing mass, which secretes proteins that degrade tissue, uses angiogenesis to recruit new blood vessels to supply it with nutrients. The angiogenic factor Cyr61 could be involved with this process.
“This paper describes only a glimpse of what this approach might reveal. There are many other categories of genes where expression varies between twins. We are just beginning to understand how RA is able to affect people in different ways. The newly discovered genes provide important insights into the nature of the disease and facilitate the design of novel treatment strategies for RA,” says Holoshitz.
The study was supported by the National Institutes of Health, the Arthritis Foundation, and the Office of Research and Development, Department of Veterans Affairs.
The lead authors were Christian S. Haas, M.D., a research fellow in the department of internal medicine at U-M Medical School; and Chad J. Creighton, a research assistant in the department of pathology at U-M Medical School. Additional contributing authors from the U-M Medical School were Xiujun Pi, M.D., Ph.D., a research fellow in the department of rheumatology; Ira Maine, Ph.D., research associate in the department of pathology; Alisa E. Koch,M.D., professor of rheumatology and internal medicine, Song Ling, Ph.D., a research investigator in the department of internal medicine; Arul M Chinnaiyan, M.D., Ph.D., an associate professor of pathology and urology. G. Kenneth Haines, III, M.D. from Northwestern University Feinberg Medical School also contributed.
