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【资讯翻译】可以预防2型糖尿病的基因突变

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发表于 2014-3-4 09:07:56 | 显示全部楼层 |阅读模式
Genetic mutations discovered that could prevent type 2 diabetes

Almost 26 million children and adults in the US have diabetes, while 79 million of us have pre-diabetes. Now, researchers have identified rare mutations in a gene that they say could prevent type 2 diabetes - the most common form of the disease - even in people who have risk factors for the condition.
The international research team, led by investigators from the Broad Institute of the Massachusetts Institute of Technology and Harvard, and the Massachusetts General Hospital, recently published the findings in the journal Nature Genetics.
The researchers say that if a drug can be created that mimics the protective effects of these mutations, this could open the doors to the prevention of type 2 diabetes.
To reach their findings, the investigators analyzed the genes of 150,000 individuals over five ancestry groups using next-generation sequencing.
All participants had severe risk factors for diabetes, including advanced age and obesity. However, none of the subjects had developed the condition and had normal blood sugar levels.
Mutations in SLC30A8 gene reduce type 2 diabetes risk by 65%
An initial analysis of individuals from Sweden and Finland revealed a mutation in a gene called SLC30A8 that stopped it from functioning - a discovery the research team found surprising. Previous studies in mice had shown that mutations in this gene increased the risk of type 2 diabetes.
Further analysis of subjects from Iceland led to the discovery of a second mutation in the SLC30A8 gene that also halted its function. This particular mutation reduced the risk of type 2 diabetes and decreased blood sugar in subjects without diabetes with no negative outcomes.
Most recently, the investigators set out to see whether these mutations discovered in the SLC30A8 gene could be found in a wider population, so assessed the genotypes of individuals from multiple ethnicities.
This led to the discovery of a further ten mutations in the SLC30A8 gene that reduced the risk of type 2 diabetes.
The research team combined all of the results to find that inheriting one copy of a mutated SLC30A8 gene reduced the risk of type 2 diabetes by 65%.
Further laboratory analysis revealed that the mutations found in SLC30A8 disrupt the normal function of ZnT8.
ZnT8 is a protein encoded by SLC30A8 that carries zinc into beta cells that produce insulin. Once zinc is in these beta cells, it plays an important part in insulin crystallization. But the researchers say they have yet to discover how a reduction in ZnT8 reduces the risk of type 2 diabetes.
Commenting on the findings, co-author Tim Rolph, vice president and chief scientific officer of Cardiovascular, Metabolic & Endocrine Disease Research at Pfizer Inc, says:
"Through this partnership, we have been able to identify genetic mutations related to loss of gene function, which are protective against type 2 diabetes.
Such genetic associations provide important new insights into the pathogenesis of diabetes, potentially leading to the discovery of drug targets, which may result in a novel medicine."
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After analyzing the genotypes of more than 150,000 individuals, researchers discovered mutations in the SLC30A8 gene that they say reduce the risk of type 2 diabetes by 65%.


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发表于 2014-3-5 10:35:15 | 显示全部楼层
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发表于 2014-3-20 08:16:05 | 显示全部楼层
  在美国,约2,600万成人、儿童被确诊为糖尿病患者,约7,900万人有糖尿病前期症状。近日,研究者识别出一种罕见的基因突变,可以预防最常见的糖尿病——2型糖尿病,即使是那些糖尿病患病风险极高的人群。
  
  这个国际研究团队由麻省理工大学和哈佛大学的博大研究所、麻省综合医院的专家组成,日前这个新成果已发表于《自然-遗传学》(Nature Genetics)杂志。

  研究组表示,如果能研发出一种药物来模拟保护这个突变基因,那我们将开启预防2型糖尿病时代的新篇章。

  为得到准确的研究成果,研究组运用新一代测序技术分析了5代人近15万人次的基因。所有受试者都存在高龄、肥胖症等糖尿病高风险因素,他们的经济收入不高,没有稳定的血糖值。

SLC30A8基因突变可使2型糖尿病患病风险降低65%

  研究初期,受试者主要来自于瑞典以及芬兰,研究组意外地发现,SLC30A8基因突变会阻断糖尿病的发生,而之前在白鼠身上进行的相关实验曾显示,这个突变则产生截然相反的效果。

  在进一步的研究中,研究组发现来自于冰岛的受试者在SLC30A8第二次基因突变后同样能阻止糖尿病的发生。这个特殊的基因突变显著地降低了2型糖尿病的患病风险,并且能使正常人在毫无副作用的情况下降低血糖值。

  因此,研究组计扩大了调查范围,他们对多个种族的个体基因进行了评估,了解他们是否都存在SLC30A8基因突变。研究团队综合所有实验数据发现,遗传SLC30A8基因突变可降低罹患2型糖尿病风险近65%。

  更多的实验室分析结果显示,SLC30A8基因突变可破坏ZnT8的正常功能。ZnT8是由SLC30A8编码而成的蛋白质,转运锌至β细胞从而产生胰岛素,是胰岛素结晶化的重要组成部分。但研究者表示他们仍未破解ZnT8的减少是如何降低2型糖尿病的患病风险的。

  辉瑞公司副总裁,心血管、内分泌&代谢疾病研究中心主任Tim Rolph评论说:“通过这次合作,我们已经可以识别这种能有效预防2型糖尿病的基因突变了。这种遗传相关性为糖尿病的发病机制提供了新观点,带动了药物靶标的研发,为制药公司开辟了新前景。”
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