TREX1：狼疮相关基因

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TREX1：狼疮相关基因

Genetic Mutations Linked To Lupus

Science Daily — A gene discovered by scientists at Wake Forest University School of Medicine has been linked to lupus and related autoimmune diseases. The finding, reported in Nature Genetics, is the latest in a series of revelations that shed new light on what goes wrong in human cells to cause the diseases.\"This research is a huge leap toward understanding the cause of lupus and related autoimmune diseases,\" said Fred Perrino, Ph.D., a co-author on the paper and a professor of biochemistry at Wake Forest. \"There had been few clues before now.\"
\"We've known that lupus was a complex disease, but now we have a specific protein and a particular cellular process that appears to be one of the causes,\" said Perrino. \"We're connecting the dots to understand the biology of what's going on with the disease.\"
In Nature Genetics, lead author Min Ae Lee-Kirsch, M.D., from the Technische Universit鋞 Dresden in Dresden, Germany, and colleagues report finding variations of the TREX1 gene discovered by Perrino in patients with systemic lupus erythematosus. The study involved 417 lupus patients from the United Kingdom and Germany. Mutations were found in nine patients with lupus and were absent in 1,712 people without lupus.
Our data identify a stronger risk for developing lupus in patients that carry variants of the gene,\" said Lee-Kirsch.
In recent years, the gene was also linked to Aicardi-Goutieres syndrome, a rare neurological disease that causes death in infants, and to chilblain lupus, an inherited disease associated with painful bluish-red skin lesions that occur during cold weather and usually improve in summer. The current research also links it to Sjogren's syndrome, a form of lupus.
The gene manufactures a protein, also known as TREX1, whose function is to \"disassemble\" or \"unravel\" DNA, the strand of genetic material that controls processes within cells. The \"unraveling\" occurs during the natural process of cells dying and being replaced by new cells. If a cell's DNA isn't degraded or unraveled during cell death, the body develops antibodies against it.

\"If the TREX1 protein isn't working to disassemble the DNA, you make antibodies to your own DNA and can end up with a disease like lupus,\" said Perrino.
In a study reported in April in the Journal of Biological Chemistry, researches found that three variations of the gene reduced the activity of the protein by four- to 35,000-fold.
The researchers hope that understanding more about the gene's mutations and the structure of the protein may lead to drug treatments to help ensure that mutant copies of the gene are inactive.
Science Daily8月1日报道，美国威克森林大学医学院的科学家们发现了与红斑狼疮及其相关自身免疫性疾病有关的基因TREX1。这项发表在《自然遗传学》上的报告，是一系列有关揭示此类疾病的细胞异常的最新发现。研究者们希望通过对该基因突变和相关蛋白结构的深入了解可以开发出有效的药物治疗来抑制突变基因的激活。

该文的第一作者、来自德国Technische Universit鋞 Dresden的Min Ae Lee-Kirsch, M.D.和他的同事们报道，从系统性红斑狼疮患者体内发现的TREX1基因上，他们发现了相关的变异。研究包括了来自英国和德国的417名狼疮患者，发现其中有9名患者带有这种基因突变，而1712名非狼疮患者则一个都没有发现。这个基因能够产生TREX1蛋白，后者的功能就是分解或解开控制细胞内各种过程的遗传物质DNA。分解过程发生在细胞死亡和更新的自然程序中，如果DNA 在细胞死亡的过程中不能更新或是解链，体内就会产生相应的抗体。如果TREX1蛋白不能将DNA解链，那您的身体就会产生针对你体内DNA 的抗体，结果就是发生狼疮等疾病。

威克森林大学生物化学教授同时也是这篇文章的合作写者（co-author？）Fred Perrino, Ph.D说：“这项研究对于明确狼疮及其相关的自身免疫性疾病是一个很大的飞跃，在此之前，相关的线索很少。我们都知道狼疮是一个复杂的疾病，但是现在我们发现了一个特殊的蛋白和一个特定的细胞过程（process），它们很可能是疾病的发病原因，我们正在试图将所有的线索联系起来去发现疾病的生物学基础。” 发表在四月份《生物化学杂志》上的一个报道显示，有研究者发现该基因的三个变异使TREX1蛋白的活力减少到40，000至35，000分之一。

在近几年，还发现这个基因与一种在婴儿期就致死的罕见的神经疾病Aicardi-Goutieres综合征有关；也与冻疮样狼疮有关，该病是一种遗传性疾病，表现为在寒冷天气发生的痛性皮肤蓝红斑，通常在夏天会缓解；研究显示该基因也与干燥综合征有关，它是狼疮的分型之一