Ahn Sun-Young, Gupta Charu
Department of Nephrology, Children's National Health System, Washington, DC, United States.
The George Washington University School of Medicine, Washington, DC, United States.
Front Pediatr. 2018 Jan 22;5:285. doi: 10.3389/fped.2017.00285. eCollection 2017.
The heritability of hypertension (HTN) is widely recognized and as a result, extensive studies ranging from genetic linkage analyses to genome-wide association studies are actively ongoing to elucidate the etiology of both monogenic and polygenic forms of HTN. Due to the complex nature of essential HTN, however, single genes affecting blood pressure (BP) variability remain difficult to isolate and identify and have rendered the development of single-gene targeted therapies challenging. The roles of other causative factors in modulating BP, such as gene-environment interactions and epigenetic factors, are increasingly being brought to the forefront. In this review, we discuss the various monogenic HTN syndromes and corresponding pathophysiologic mechanisms, the different methodologies employed in genetic studies of essential HTN, the mechanisms for epigenetic modulation of essential HTN, pharmacogenomics and HTN, and finally, recent advances in genetic studies of essential HTN in the pediatric population.
高血压(HTN)的遗传力已得到广泛认可,因此,从基因连锁分析到全基因组关联研究等广泛的研究正在积极进行,以阐明单基因和多基因形式高血压的病因。然而,由于原发性高血压的复杂性,影响血压(BP)变异性的单个基因仍然难以分离和识别,这使得单基因靶向治疗的开发具有挑战性。其他致病因素在调节血压中的作用,如基因-环境相互作用和表观遗传因素,正越来越受到关注。在这篇综述中,我们讨论了各种单基因高血压综合征及其相应的病理生理机制、原发性高血压遗传研究中采用的不同方法、原发性高血压的表观遗传调节机制、药物基因组学与高血压,最后讨论了儿科人群原发性高血压遗传研究的最新进展。