Genetics of salt-sensitive hypertension

Abstract

Excess dietary salt intake represents a predominant cause of hypertension. However, individual blood pressure response to salt is heterogeneous, possibly due to different inherited susceptibility. The early identification of rare monogenic forms of hypertension associated with abnormalities of renal tubular sodium handling and response to diuretics highlighted the important role of renal alterations in salt-sensitive hypertension. Thereafter, interest has concentrated on the identification of more common allelic variants of candidate genes for hypertension in relation to the salt-sensitivity phenotype. By now, relatively large numbers of such variants have been described, and the pathogenic role of gene-gene interaction has received increasing attention. The alternative approach, consisting of the search for quantitative trait loci in the human genome linked to the transmission of salt-sensitive hypertension, has so far been less successful and cost-effective. This review summarizes consolidated knowledge and discusses the most recent novel findings on the impact of genetic variance on salt-sensitivity of blood pressure.

Hypertension: Salt restriction, sodium homeostasis, and other ions

“…[24,25] This further strengthens the concept that Na + intake in hypertensives can never be a fixed quantity for all humans as it is genetically (mono as well as polygenetically) determined also. Besides evidence also indicates that complex interactions among multiple genes might also affect the salt sensitivity of an individual.…”

“…Besides evidence also indicates that complex interactions among multiple genes might also affect the salt sensitivity of an individual. [24,25] There is no unanimity and consensus in the definition of salt sensitivity from the available literature so far. [26][27][28] However, Weinberger [28] classified salt sensitive individuals as those in whom there is 10% increase in mean arterial pressure when the low (9 mmol/day) and high salt (249 mmol/day) pressures were compared.…”

Salt craving: The psychobiology of pathogenic sodium intake

“…In the absence of any other manipulation, it has been shown that high sodium intake alone can promote hypertension in rats, chimpanzees, pigs, and African Green Monkeys [36,[50][51][52][53][54]. Both human and animal studies have provided evidence that there may be a strong genetic component underlying the susceptibility to salt-sensitive hypertension [52,[55][56][57].…”

Polymorphisms ofEDNRB,ATG, andACEgenes in salt-sensitive hypertensionThis article is one of a selection of papers published in the special issue (part 2 of 2) on Forefronts in Endothelin.

“…Several studies have been performed to identify genetic factors that may contribute to salt sensitivity, but the results have not been consistent (Strazzullo and Galletti 2007), possibly due to the difficulty in defining the phenotype. To overcome this problem, a homogeneous population of SS and SR hypertensive patients and normotensive controls was recruited that did not differ for ethnicity, age, sex, or body mass index.…”