doi: 10.1161/01.RES.0000269420.81524.05
© 2007 American Heart Association, Inc.
Editorials |
The Challenge of Genetic Studies in Hypertension
From the Section on Pharmacology, Division of Intramural Research Programs, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda, Md.
Correspondence to Juan M. Saavedra M.D., Section on, Pharmacology, DIRP, NIMH, NIH, DHHS, 10 Center Drive, Building 10, Room, 2D-57, Bethesda, MD 20892. E-mail saavedrj@mail.nih.gov
See related article, pages 1522–1529
Key Words: endothelin • VEGF • human hypertension • haplotype analysis • salt sensitivity
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Essential hypertension is the most common cardiovascular disease,1,2 with genetic elements contributing up to 30% to 50% of the blood pressure variability.3 Identifying contributing genes may allow us to recognize vulnerable individuals, to classify patients in subgroups with definite genetic and pathogenic mechanisms and to achieve better prevention and therapeutics. Using knowledge of pathways involved in cardiovascular regulation, many genes have been implicated in the pathophysiology of hypertension by the candidate gene linkage approach. The approach relies on studies of single nucleotide polymorphic (SNP) markers, in most cases derived from experimental rodent models of the disease. Genes responsible for vasoactive peptides, their receptors, and sodium homeostasis have taken center stage because of the role of these processes in the regulation of fluid volume and vascular reactivity.
However, in spite of intense efforts (11 199 publications for "human hypertension/genetics" listed in PubMed by April 2007) the attempts to replicate association studies have not been encouraging. The question has been raised as to whether high impact journals should even publish these studies.4 The reasons for this problem are clear. Blood pressure is controlled by a complex combination of processes with redundant balancing pressor and depressor mechanisms. Hypertension is a polygenetic condition with multiple interactions of networked genes, strongly influenced by environmental factors. Genes and the environment affect the onset, severity, progression, prognosis and treatment of the disease, and their influence differs among ethnic groups or even population subgroups.1,2 Our knowledge of the mechanisms of blood pressure control and the pathogenesis of hypertension
Related Article:
Circ. Res. 2007 100: 1522-1529.