A Candidate Hypertension Gene

Abstract

See related article, pages 992–999 Hypertension affects >20% of the general population, and yet its etiologic basis remains unknown in the vast proportion of those affected.1 Hypertension greatly increases the risk of stroke, myocardial infarction, congestive heart failure and renal dysfunction thus making it an important focus of clinical research. Although pharmacological reductions in blood pressure have been shown to decrease the incidence of these adverse consequences,2 large numbers of hypertensive patients go undiagnosed, undertreated, or are nonresponsive to lifestyle modifications and medical therapy.1 As such, there remains a pressing need for an improved understanding of the mechanisms underlying hypertension. Recent advances in genomic and proteomic analyses have led to the discovery of Mendelian forms (monogenetic traits) of hypertension.3,4 Although rare, these mutations which mainly involve altered renal salt handling, provide a molecular basis for understanding the critical role of the kidney during normal blood pressure regulation.5 By contrast, our understanding of the relative contributions of kidney, heart, CNS, and blood vessel function to blood pressure variations in the general population is complicated by the fact that spontaneous hypertension typically arises as a complex quantitative trait affected by differing combinations of genetic and environmental factors. A number of quantitative trait loci (QTL) associated with hypertension have been identified in both animal disease models and human patients, however the affected gene(s) at these sites have remained elusive owing to the large size and complexity of the regions identified.6 The use of congenic rodent strains to reduce the genomic size of QTLs is an important advance in the field (Reviewed in 7). Indeed, an article in this issue of Circulation Research highlights the potential of …