目前已知有超过30个基因参与体重调控，这些基因一旦发生损伤性变化会导致极端肥胖情况的出现。类似的，一些基因一旦出现变异可能导致人们患2型糖尿病。目前科学界还不清楚因为遗传而导致的极端肥胖和2型糖尿病到底占多大比例，但是可以确定的是这些情况与囊胞性纤维症和亨廷顿氏舞蹈症一样能够遗传。

伦敦大学皇家理工学院的研究人员近日发现了肥胖和2型糖尿病的一种新遗传形式。研究人员通过对一位极端肥胖的年轻女性及其家人的DNA进行排序，发现了这种新的缺陷基因。

这位女性从童年开始，因为食欲格外旺盛导致极度肥胖，患有2型糖尿病、学习困难症并且面临生育方面的问题。工作人员发现一种突变的基因导致她不能合成一种名为羧基肽酶-E（CPE）的蛋白质。CPE是一种酶，对许多激素以及大脑信号传导的正常运行发挥重要作用。而这些激素和大脑信号则控制着食欲、胰岛素以及其他在生殖系统中发挥重要作用的激素。

尽管已有证据证实CPE缺陷会导致小鼠肥胖、糖尿病和记忆障碍，但之前并没有在人类中发现这种情况。因为CPE是一种隐性性状，一个人必须从他的父母亲中都遗传到一个变异的该基因才会受到影响。内分泌咨询专家Tony Goldstone医生，曾为这名女性患者进行遗传咨询，得知患者的父母是表亲，这使她从双亲中遗传到相同变异基因的可能性更高，另外她有一个患有相同病症的哥哥在21岁时去世。

译者解释：

关于隐性性状，科学的解释大家可以去看书。通俗的来说就是下图表现的。

B和b是控制相同性状的基因，如B代表有酒窝，b代表没酒窝，当B和b碰到一起时，B占上风，性状显示仍然是有酒窝，这个时候b虽然存在但是其代表的没有酒窝的性状却没有表现出来。从图中可以看出这对父母的子代有酒窝的可能性是75%，没有酒窝的可能性是25%。

bb碰到一起的概率在这种情况下本来就小，文中提到的女性患者，导致其肥胖的基因还是因为基因突变导致的，基因突变的随机性很大，所以碰到相同突变的2个隐性基因正好相遇其实并不是那么简单。然而……近亲后代遇到这种情况的可能性就大很多。这也是为什么我们不允许近亲结婚的原因了。

负责此项基因测试同时也是该研究的第一作者Sanne Alsters博士称，“为患者的病情找到一个遗传原因可以帮助她和她的家庭更好的了解和处理她的病情。在她的亲属中，有些人仅有一个该缺陷基因，我们可以对他们进行观察。仅有一个缺陷基因可能使他们获得的肥胖风险没有那么明显。”

皇家理工学院医学院教授，也是这项研究的负责人Alex Blakemore表示：“目前被发现的可以导致的肥胖和糖尿病的单一基因越来越多。我们也不知道未来还会发现多少，也不知道极端肥胖人群中有多少比例的人们是患有这种疾病——因为我们仅通过肉眼观察是无法分辨的。”

“基因缺陷导致的肥胖是非常严重的失调情况，身体调节饥饿和饱腹信号的能力被影响。这种情况和其他遗传疾病的遗传机制是一样的。患者不应因此受到歧视，我们应该为他们提供遗传咨询和终身特别支持，使他们能够尽可能的过上健康的生活。”Blakemore教授称基因测序应该在极端肥胖的父母中被广泛使用。她说：“如果有人携带了某种可以导致肥胖的突变基因，我们寻找携带可以导致其他病症的突变基因的人，如果他们需要的话可以为他们和他们的家人提供遗传咨询。对于患者来说这种诊断是非常有价值的。这将有助于设定符合现实情况的预期，也能帮助他们得到尽可能好的治疗。”

该研究发表在公共科学图书馆期刊上，这个杂志是由英国国家健康研究所皇家生物医学研究中心和英国糖尿病协会支持的。

翻译：朱晓倩 为了方便阅读调整了一些段落顺序

来源：Imperial College London. (2015, June 30). New genetic form of obesity, diabetes discovered. ScienceDaily. Retrieved July 1, 2015 from www.sciencedaily.com/releases/2015/06/150630080159.htm

Scientists have discovered a new inherited form of obesity and type 2 diabetes in humans.

A large number of genes are involved in regulating body weight, and there are now over 30 genes known in which people with harmful changes in DNA sequence become extremely overweight. Similarly, there are a number of genes that can, when altered, cause type 2 diabetes. These conditions are inherited through families in exactly the same way as disorders such as cystic fibrosis or Huntington's disease.

It is unclear what proportion of severe obesity and type 2 diabetes is caused by genetic disease.

Researchers at Imperial College London discovered the new defect by sequencing the DNA of an extremely obese young woman and members of her family. In addition to an increased appetite leading to severe weight problems from childhood, she had type 2 diabetes, learning difficulties, and reproductive problems.

They found that she had inherited two copies of a harmful genetic change that meant she could not make a protein called carboxypeptidase-E (CPE). This is an enzyme that is important in the proper processing of a number of hormones and brain transmitters controlling appetite, insulin and other hormones important in the reproductive system.

Studies have previously shown that CPE deficiency causes obesity, diabetes, and impaired memory in mice, but no humans with the condition have been found before. CPE deficiency is a recessive condition, so a person would need to inherit the altered genetic sequence from both parents to be affected.

The study, published in the journalPLOS ONE, was funded by the NIHR Imperial Biomedical Research Centre and Diabetes UK.

Professor Alex Blakemore from the Department of Medicine at Imperial College London, who led the study, said: "There are now an increasing number of single-gene causes of obesity and diabetes known. We don't know how many more have yet to be discovered, or what proportion of the severely obese people in our population have these diseases -- it is not possible to tell just by looking.

"These are serious disorders that affect the body's ability to regulate hunger and fullness signals. They are inherited in the just same way as other genetic diseases and the sufferers should not be stigmatised for their condition. They should be offered genetic counselling and specialised lifelong support to allow them as healthy a life as possible."

The patient was clinically evaluated by consultant endocrinologist Dr Tony Goldstone, who runs a specialist genetics obesity clinic at Hammersmith Hospital. The patient's parents are cousins, giving her a relatively high likelihood of inheriting the same genetic change from both parents. She had an older brother with similar symptoms who died aged 21.

The first author Dr Sanne Alsters, also in the Department of Medicine, who carried out the genetic tests, said: "Finding a genetic cause for the patient's problems has helped her and her family to understand and manage her condition better. We can also look at members of her family with one abnormal copy of the gene, to see they are affected in more subtle ways that could increase their risk of obesity."

Professor Blakemore said genetic tests should be widely available for patients with severe obesity. "If people are diagnosed with a genetic condition like this one, we can look for other possible symptoms, and offer genetic advice to other family members if they want this. Diagnosis is very valuable to the patient. It helps to set realistic expectations, and can help them get the best possible treatment," she said.