O'Connor D T, Insel P A, Ziegler M G, Hook V Y, Smith D W, Hamilton B A, Taylor P W, Parmer R J
Departments of Medicine and Pharmacology and Center for Molecular Genetics, University of California, San Diego, and VA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA.
Curr Hypertens Rep. 2000 Feb;2(1):16-22. doi: 10.1007/s11906-000-0053-8.
Because the complex phenotype of human hypertension is at least in part genetically determined, how individual genes ultimately contribute to the disease is not well understood. By contrast, intermediate phenotypes are traits associated with complex disease, but which may display simpler genetic properties such as greater heritability, more consistent and earlier penetrance and bimodality, and may suggest particular candidate susceptibility genes. Because autonomic nervous system activity is altered in hypertension, we examined biochemical, physiologic, and pharmacologic autonomic traits that fulfill at least some of these properties. Such biochemical, physiologic, or pharmacologic autonomic traits may be especially valuable as phenotypic anchor points in linkage or association studies probing the genetic basis of human hypertension.
由于人类高血压的复杂表型至少部分是由基因决定的,所以个体基因最终如何导致该疾病尚未得到充分了解。相比之下,中间表型是与复杂疾病相关的性状,但可能表现出更简单的遗传特性,如更高的遗传力、更一致和更早的外显率以及双峰性,并且可能提示特定的候选易感基因。由于高血压患者的自主神经系统活动会发生改变,我们研究了满足至少其中一些特性的生化、生理和药理自主性状。在探究人类高血压遗传基础的连锁或关联研究中,此类生化、生理或药理自主性状作为表型锚定点可能特别有价值。