生物谷報(bào)道：牛津大學(xué)Wellcome Trust人類基因?qū)W中心（WTCHG）的科學(xué)家發(fā)現(xiàn),，調(diào)解人體24小時(shí)節(jié)律的DNA同時(shí)也可以控制血壓,。
以上結(jié)果表明對(duì)生物功能節(jié)律性的改變將增加患心血管疾病和糖尿病的風(fēng)險(xiǎn),。這一由Wellcome Trust基金支持的研究利用老鼠模型和人類的基因?qū)W研究證實(shí)了在生物鐘基因變化和患心血管疾病之間存在的關(guān)系。研究結(jié)果發(fā)表在本周的《Proceedings of the National Academy of Science》上,。
之前針對(duì)心血管疾病和糖尿病的其它研究已證實(shí)它們之間存在某種程度的聯(lián)系,，但牛津大學(xué)的研究首次提出了基因?qū)W證據(jù)。
眾所周知很多關(guān)鍵的生物功能,，包括體溫,、睡眠節(jié)律、進(jìn)食,、血壓,、血糖及很多神經(jīng)和激素調(diào)節(jié)都表現(xiàn)出24小時(shí)周期節(jié)律。對(duì)于一些疾病也是如此,，例如心臟病和中風(fēng)（常發(fā)生于清晨）以及某些精神疾病,。
BMAL1是調(diào)控身體分子鐘的關(guān)鍵基因。一旦BMAL1不再活躍,，生物鐘就會(huì)停止工作,，而血壓、血糖濃度,、體重和新陳代謝都會(huì)發(fā)生變化,。此項(xiàng)研究提供了直接證據(jù)證實(shí)BMAL1的變化和高血壓有關(guān)。這也是首次有證據(jù)顯示人類生物鐘變化和2型糖尿病,、高血壓之間存在直接聯(lián)系,。
研究還突出了跨物種研究對(duì)證實(shí)新假說(shuō)的重要性。研究負(fù)責(zé)人Dominique Gauguier教授表示：“生物節(jié)律調(diào)節(jié)對(duì)于多種生物過(guò)程都很重要,，這類基因研究可能將擴(kuò)展到其它疾病領(lǐng)域,。”研究結(jié)果可能對(duì)疾病治療產(chǎn)生影響，因?yàn)樯眢w對(duì)藥物的反應(yīng)和生物鐘有關(guān),。 （教育部科技發(fā)展中心）
鏈接http://www.physorg.com/news107778760.html
原始出處:
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.
