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【Science】睡眠基因突变增加患病风险
By Gretchen Vogel
ScienceNOW Daily News
8 December 2008
Is there a link between sleep and type 2 diabetes? That's one implication of a new study, which has found that variants in a gene that helps regulate the body's daily rhythms increase the chance of developing the disease. The find, reported online yesterday in three papers in Nature Genetics, may suggest new ways to treat or prevent the ever more common disorder.
The body's internal clock--or circadian rhythm--is kept accurate by a hormone called melatonin, whose levels fall during the day and rise at night. Melatonin helps regulate sleep patterns, and in recent years, scientists have found that these patterns are tied to metabolism. For example, people who sleep less have a higher risk of obesity and diabetes. And experimental mice with disrupted circadian rhythms tend to gain weight.
Researchers suspect the link has something to do with another hormone, insulin: Melatonin appears to regulate the body's levels of insulin, which helps cells take up the sugar glucose from the blood. (In type 2 diabetes, the system doesn't work properly, and blood glucose is too high, damaging various organs.)
The new studies back up this link. Three groups found that people with certain variations in the so-called melatonin receptor 2 gene have higher levels of blood glucose first thing in the morning. Such high fasting glucose levels are one warning sign for type 2 diabetes. Gonçalo Abecasis of the University of Michigan, Ann Arbor, and his colleagues used data from 10 genome-wide studies involving 36,610 individuals to look for genetic variations that correlated with fasting glucose concentrations. They pinpointed a common variation in the gene called MTNR1B, which codes for one of the body's two known melatonin receptors. A study led by Leif Groop of Lund University in Sweden, using data from two long-term health studies, confirmed that result and also found that people carrying the high-blood-sugar gene variant have an increased risk of developing type 2 diabetes. Philippe Froguel of Imperial College London and his colleagues, looking at data from 2154 individuals in France, found a similar association with a different genetic variation very near the same gene.
Although previous work had suggested a connection between metabolism and circadian rhythm control, the find "will come as a big surprise to 99% of people involved in diabetes research," says Eve Van Cauter of the University of Chicago in Illinois, an expert on sleep and metabolism who was not involved in the studies. The exact biological explanation is not yet clear; however, she says one possibility is that people with the high-risk gene variant have an insulin-production system that is overly sensitive to melatonin. Understanding exactly what effect the variations have could help design more effective treatments for diabetics, says Froguel.
睡眠基因突变增加患病风险
Gretchen Vogel
ScienceNOW Daily News
2008年12月8日
睡眠与2型糖尿病之间存在某种联系吗？一项新的研究对此得出了肯定的答案，该研究同时发现，一种控制身体日常生理节奏的基因产生的突变增加了罹患糖尿病的几率。这一发现可能意味着治疗或预防这种越来越常见的疾病的新方法即将问世。
人体的生物钟，或者说生理节奏，是由一种名为退黑激素的荷尔蒙精确调控的，这种荷尔蒙的水平在白天会降低，而在夜晚则会升高。退黑激素帮助调节睡眠模式，在最近的几年里，科学家发现，这些睡眠模式依赖于人体的新陈代谢。例如，那些睡眠较少的人容易罹患糖尿病和肥胖症。同时那些生理节奏紊乱的实验室小鼠则更容易体重增加。
研究人员由此推测，这种联系可能与另一种荷尔蒙，即胰岛素有关。退黑激素似乎能够调节身体中的胰岛素水平，后者有助于细胞从血液中吸收葡萄糖。而在2型糖尿病患者体内，这套系统并不能正常的工作，从而导致血液中的葡萄糖水平升高，最终危害其他的器官和组织。
新的研究成果支持了这种联系。3个研究小组发现，每天一大早，那些所谓的退黑激素受体2型基因产生某种变异的人，其血液中的葡萄糖含量都比较高。这种空腹高血糖现象是罹患2型糖尿病的一个信号。美国安阿伯市密歇根大学的Gon?alo Abecasis和同事，利用包括36610名个体在内的10个全基因组研究的数据，寻找了与空腹血糖水平有关的遗传变异。最后研究人员在一个名为MTNR1B的基因——负责编码已知两种人体退黑激素受体中的一种——中找到了一个常见的变异。另一项由瑞典Lund大学的Leif Groop领导的研究，则利用来自两项长期健康研究的数据证明了这一结果，该研究同时发现，那些携带了高血糖基因变异的人也容易患上2型糖尿病。英国伦敦皇家学院的Philippe Froguel和他的同事利用来自法国的2154名个体的数据，在MTNR1B基因的附近又发现了一种与不同的遗传变异有关的类似关联。研究人员在最新出版的英国《自然—遗传学》杂志上报告了这3项研究成果。
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作者:admin@医学,生命科学 2011-02-17 05:11
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