Harrap Stephen B
Department of Physiology, University of Melbourne, Victoria, Australia.
J Am Soc Hypertens. 2009 Jul-Aug;3(4):231-7. doi: 10.1016/j.jash.2009.06.001.
This review briefly charts the recent history of the genetic study of high blood pressure (BP). After an inconsistent start it was hoped that very large genome-wide association studies (GWAS) might be able to provide some reliable answers. The two largest and most recent GWAS: CHARGE and GlobalBPgen were able to identify, despite some significant inconsistencies, genetic loci that accounted for only about 2% of the genetic factors believed to influence BP. The loci were associated with an estimated effect on BP of 1 mm Hg or less. No doubt many other loci exerting even smaller (<0.5 mm Hg) exist. This review contends that it is time to focus on the loci that can be viewed as confirmed, rather than extending the GWAS searches for less significant genetic influences. It is time to identify the precise deoxyribonucleic acid variants affecting BP, understand their mechanisms of action and think of ways in which such knowledge can be used to prevent and treat high BP in novel, effective, and possibly tailored ways.
本综述简要梳理了高血压遗传学研究的近期历程。在起步阶段结果参差不齐之后,人们曾寄希望于大规模全基因组关联研究(GWAS)或许能够提供一些可靠答案。两项规模最大且最新的GWAS研究:CHARGE和GlobalBPgen,尽管存在一些显著的不一致之处,但仍能够识别出一些遗传位点,这些位点仅占据信影响血压的遗传因素的约2%。这些位点与血压的估计效应为1毫米汞柱或更低。毫无疑问,还存在许多其他效应甚至更小(<0.5毫米汞柱)的位点。本综述认为,现在是时候专注于那些可被视为已确认的位点,而不是扩大GWAS搜索以寻找不太显著的遗传影响。现在是时候识别影响血压的精确脱氧核糖核酸变异,了解其作用机制,并思考如何以新颖、有效且可能是量身定制的方式利用这些知识来预防和治疗高血压了。