摘要：一个由伦敦国王学院和牛津大学领导的研究小组发现了一个基因，它与2型糖尿病以及胆固醇水平有关，事实上，这是一个 “总开关”基因，控制了与肥胖相关的其他基因的行为。该研究结果发表于5月15日的《自然-遗传学》，将有助于人类研究出治疗肥胖相关疾病的更有效药物。
英国伦敦大学国王学院与牛津大学科学家牵头这一研究。他们认为，脂肪在人体对肥胖、心脏病和糖尿病等新陈代谢疾病易感性方面起关键作用，因此，找到其中的调节基因可能有助研究对抗这些疾病的新方法。
科学家们从800名英国女性双胞胎身上提取皮下脂肪样本，分析其中超过２万个基因。他们发现，一种名为KLF14的基因与皮下脂肪内多种基因水平有关，这表明，KLF14是控制这些基因的“总开关”。
科学家说，这些受KLF14控制的基因与新陈代谢特点，即身高体重指数、肥胖、胆固醇、胰岛素和葡萄糖水平有关。
接下来，科学家分析从冰岛人身上提取到的600份基因样本，进一步肯定这一发现。
'Master Switch' Gene for Obesity and Diabetes Discovered
Published May 15 in Nature Genetics, the study was one part of a large multi-national collaboration funded by the Wellcome Trust, known as the MuTHER study. It involves researchers from King's College London, University of Oxford, The Wellcome Trust Sanger Institute, and the University of Geneva. DeCODE Genetics also contributed to the results reported in this paper.
It was already known that the KLF14 gene is linked to type 2 diabetes and cholesterol levels but, until now, how it did this and the role it played in controlling other genes located further away on the genome was unknown.
The researchers examined over 20,000 genes in subcutaneous fat biopsies from 800 UK female twin volunteers. They found an association between the KLF14 gene and the expression levels of multiple distant genes found in fat tissue, which means it acts as a master switch to control these genes. This was then confirmed in a further independent sample of 600 subcutaneous fat biopsies from Icelandic subjects.
These other genes found to be controlled by KLF14 are in fact linked to a range of metabolic traits, including body-mass index (obesity), cholesterol, insulin and glucose levels, highlighting the interconnectedness of metabolic traits.
The KLF14 gene is special in that its activity is inherited from the mother. Each person inherits a set of all genes from both parents. But in this case, the copy of KLF14 from the father is switched off, meaning that the copy from the mother is the active gene -- a process called imprinting. Moreover, the ability of KLF14 to control other genes was entirely dependent on the copy of KLF14 inherited from the mother -- the copy inherited from the father had no effect.
Professor Tim Spector from the Department of Twin Research at King's, who led the MuTHER project, said: 'This is the first major study that shows how small changes in one master regulator gene can cause a cascade of other metabolic effects in other genes. This has great therapeutic potential particularly as by studying large detailed populations such as the twins we hope to find more of these regulators.'
Professor Mark McCarthy from the University of Oxford, who co-led the study, said: 'KLF14 seems to act as a master switch controlling processes that connect changes in the behaviour of subcutaneous fat to disturbances in muscle and liver that contribute to diabetes and other conditions. We are working hard right now to understand these processes and how we can use this information to improve treatment of these conditions.'
