生物谷报道：牛津大学Wellcome Trust人类基因学中心（WTCHG）的科学家发现，调解人体24小时节律的DNA同时也可以控制血压。
以上结果表明对生物功能节律性的改变将增加患心血管疾病和糖尿病的风险。这一由Wellcome Trust基金支持的研究利用老鼠模型和人类的基因学研究证实了在生物钟基因变化和患心血管疾病之间存在的关系。研究结果发表在本周的《Proceedings of the National Academy of Science》上。
之前针对心血管疾病和糖尿病的其它研究已证实它们之间存在某种程度的联系，但牛津大学的研究首次提出了基因学证据。
众所周知很多关键的生物功能，包括体温、睡眠节律、进食、血压、血糖及很多神经和激素调节都表现出24小时周期节律。对于一些疾病也是如此，例如心脏病和中风（常发生于清晨）以及某些精神疾病。
BMAL1是调控身体分子钟的关键基因。一旦BMAL1不再活跃，生物钟就会停止工作，而血压、血糖浓度、体重和新陈代谢都会发生变化。此项研究提供了直接证据证实BMAL1的变化和高血压有关。这也是首次有证据显示人类生物钟变化和2型糖尿病、高血压之间存在直接联系。
研究还突出了跨物种研究对证实新假说的重要性。研究负责人Dominique Gauguier教授表示：“生物节律调节对于多种生物过程都很重要，这类基因研究可能将扩展到其它疾病领域。”研究结果可能对疾病治疗产生影响，因为身体对药物的反应和生物钟有关。 （教育部科技发展中心）
链接http://www.physorg.com/news107778760.html
原始出处:
Published online before print August 29, 2007
Proc. Natl. Acad. Sci. USA, 10.1073/pnas.0703247104
Genetics
Aryl hydrocarbon receptor nuclear translocator-like (BMAL1) is associated with susceptibility to hypertension and type 2 diabetes
( comparative genomics | genetic polymorphism | molecular clock | SNP | sequence variation )
Peng Y. Woon *, Pamela J. Kaisaki *, José Bragança *, Marie-Thérèse Bihoreau *, Jonathan C. Levy , Martin Farrall *, and Dominique Gauguier *
*Wellcome Trust Centre for Human Genetics and Department of Cardiovascular Medicine, University of Oxford, Oxford OX3 7BN, United Kingdom; and Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford OX3 7LJ, United Kingdom
Edited by Joseph S. Takahashi, Northwestern University, Evanston, IL, and approved July 26, 2007 (received for review April 8, 2007)
Many aspects of physiology and behavior follow a circadian rhythm. Brain and muscle Arnt-like protein-1 (BMAL1) is a key component of the mammalian molecular clock, which controls circadian oscillations. In the rat, the gene encoding Bmal1 is located within hypertension susceptibility loci. We analyzed the SNP distribution pattern in a congenic interval associated with hypertension in the spontaneously hypertensive rat (SHR), and we show that Bmal1 maps close to a region genetically divergent between SHR and its normotensive (Wistar–Kyoto) counterpart. Bmal1 sequencing in rat strains identified 19 polymorphisms, including an SHR promoter variant that significantly affects Gata-4 activation of transcription in transient transfection experiments. A genetic association study designed to test the relevance of these findings in 1,304 individuals from 424 families primarily selected for type 2 diabetes showed that two BMAL1 haplotypes are associated with type 2 diabetes and hypertension. This comparative genetics finding translated from mouse and rat models to human provides evidence of a causative role of Bmal1 variants in pathological components of the metabolic syndrome.
