红斑狼疮的易感基因

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Gene studies home in on lupus cause

WASHINGTON (Reuters) - Four separate studies published on Sunday identify a series of genes linked with lupus, a debilitating illness that can affect various parts of the body at once.

The studies show that, as suspected, the immune system is going haywire in lupus. But it also points to some previously unsuspected causes of the once-mysterious disease.

And the findings may not only help scientists find better treatments for the disease -- but may help in diagnosing it in the first place, as it is easily confused with other conditions.

Systemic lupus erythematosus, lupus for short, affects at least 1.4 million people in the United States and 50,000 in Britain, advocacy groups say.

It can damage the joints, kidneys, heart, lungs, brain and blood and is marked sometimes by a characteristic butterfly-shaped rash on the face.

Three studies in the journal Nature Genetics and a fourth in the New England Journal of Medicine identify several areas of DNA that carry mutations in people with lupus and their relatives.

\"These results suggest biologic pathways that help us understand the condition better and suggest additional genetic and non-genetic triggers,\" Carl Langefeld, director of the Center for Public Health Genomics at Wake Forest University in North Carolina and one of the study coordinators, said in a statement.

\"In addition, they will help delineate the genetic distinctions between rheumatoid arthritis, lupus and other autoimmune diseases, which could lead to earlier, more accurate diagnoses.\"

One international team of researchers studied the DNA of more than 6,700 women, including people with lupus, their relatives, and unrelated people with no evidence of the disease. Among the four studies, about 10,000 people were tested and 13 different genes were implicated.

\"Overall, these papers confirm what investigators have been finding over the past decades,\" said Dr. Mary Kuntz Crow of the Hospital for Special Surgery in New York.

\"They show that many aspects of the immune system are involved in the development of the disease, but they also provide a new level of detail regarding the specific molecular pathways that contribute.\"

MISSED GROUPS

Some of the genes also apparently contribute to blood vessel function and some have unknown roles, the researchers said.

In a commentary in the New England Journal of Medicine, Crow noted that the studies all miss the biggest group of people affected by lupus.

\"In the major studies, all of the subjects were of European descent, but lupus is most severe in people with African, Asian and Hispanic backgrounds,\" Crow said in a statement.

\"We need to confirm that these same genes are involved in all of our patient populations and identify any distinct genes that might be involved in those populations at greatest risk for poor outcomes.\"

Timothy Vyse of Imperial College London said the studies might help researchers develop better treatment.

\"Lupus is a complex disease, which is hard to diagnose, and it can cause many different and unpredictable problems for patients. Living with lupus can be really tough,\" Vyse said in a statement.

\"We currently can treat the disease by suppressing the immune system, but we urgently need to understand in much more detail what goes wrong with the immune system so that we can design better treatments.\"

http://www.reuters.com/article/healthNews/idUSN2033315020080120

华盛顿（路透社）——星期天公布的四个独立的研究证实了一系列的与红斑狼疮（一种可以损害全身各个脏器、系统的疾病）的发生相关的基因。正象以前假设的那样，这些试验也证明了在红斑狼疮的发生发展过程中，机体免疫系统处于一种十分紊乱的情况。但是这些试验同时提出了许多以前未曾想到的引起这种神秘疾病的原因。这些发现不仅在治疗红斑狼疮中有重要的作用，同时也为在这一疾病的早期提供更加准确的诊断并于其他疾病鉴别提供了重要的线索。系统性红斑狼疮，简称红斑狼疮。在美国，每年的患病人数是1500000，在英国，每年的患病人数是50000。这种疾病在全身的影响是十分广泛的，关节、肾、心脏、肺、脑、血液都会受到影响。在一些病人身上，还会出现特征性的蝶形红斑。3篇发表在《自然》遗传学上的文章以及1篇发表在《新英格兰医学》杂志上的文章证实了在红斑狼疮病人DNA上携带有突变基因的片段。Carl Langefeld（北卡莱罗纳州Wake Forest大学公共卫生中心主任）以及他的一位同事在一项声明中说：“这些研究更好的为我们揭示了红斑狼疮发病的生物学过程以及各种遗传学和非遗传学的致病因素。” “更重要的是这些结果将会帮助我们描绘出类风湿性关节炎、红斑狼疮等的遗传学特点，以更好的指导早期的正确诊断。”一个国际研究组的研究员们对6700名妇女的DNA进行了取样研究，这些妇女包括了那些红斑狼疮的患者、她们的亲属、与她们无血缘关系的健康妇女。在这4项研究中，样本量共有10000，研究的基因片段共有13个。Mary Kuntz Crow博士（纽约特殊外科医院）说：总体来说，这些研究结果印证了研究者们过去几十年想要找到的答案。 “他们揭示了在这一疾病过程中，免疫系统的许多环节都参与其中，但是他们同时提供了更详细层面的关于疾病发生进展的分子途径。
被忽略的群体
研究者说，这次发现的一些基因片段有些在血管的结构功能方面有明显的作用，有一些的功能则还不是十分明了。在那篇发表在《新英格兰医学》杂志上发表的文章的注释中，Crow博士指出这些研究都忽略了罹患红斑狼疮的最大的一组人群。 “在主要的研究，所有的样本都是取材于欧洲血统的人群，而忽略了红斑狼疮最大的患病群体：非洲人、亚洲人、西班牙人。” “我们需要证实这次发现的这些基因在所有红斑狼疮患者疾病的过程中都起到了一定作用，同时我们需要搞清楚在那些有高危因素以及预后相对较差的群体中，是否还有其他引起疾病发生发展的特殊基因片段。” Timothy Vyse（伦敦皇家大学）说这些研究结果会帮助研究者发现更好的对于这种疾病的治疗方法。Timothy Vyse 说:“红斑狼疮是一种十分复杂的疾病，诊断很困难，同时这种疾病会给病人造成许多不同的难以预料的问题，红斑狼疮患者的长期生存是十分艰难的。” “目前针对这种疾病的治疗方法就是抑制免疫系统，但是我们迫切的需要更多关于在疾病进程中免疫系统到底出现了怎样的问题的指示，以提供针对病因的更加有效的治疗。”