Role of CYP2C9 genetic variants for salt sensitivity and the regulation of the renin–angiotensin–aldosterone system in normotensive men

Abstract

The present study confirms an association between CYP2C9 polymorphism and activity of the RAAS. Specifically, we detected an overall effect of CYP2C9*3 on lower PRA, but not on salt-sensitive BP regulation in normotensive men. Further studies are needed to analyze the long-term effects of CYP2C9*3 for salt sensitivity and hypertensive diseases.

CYP2C9 variants and blood pressure response to salt: when salt sensitivity meets pharmacogenomics

“…The finding by Bolbrinker et al [10] that CYP2C9 Ã 3 carriers, who represent about 10% of the sample, had significantly lower PRA compared with CYP2C9 Ã 1/ Ã 1 homozygotes is in line with previous results in hypertensive patients [20]. The authors postulate that the downregulation of the RAAS would be the result of enhanced sodium reabsorption due to epoxyeicosatrienoic acid (EET)-induced epithelial sodium channel (ENaC) activation (i.e.…”

“…Power is further reduced by the fact that participants were young normotensive men, most of whom were not salt sensitive. As stated by Bolbrinker et al [10], a safe conclusion is that these CYP2C9 variants do not have a large effect (i.e. !3 mmHg) on the blood pressure response to salt in young normotensive white men.…”

“…Bolbrinker et al [10] report findings from a carefully conducted study on the association between two functional CYP2C9 variants [CYP2C9 Ã 2 (rs1799853) and CYP2C9 Ã 3 (rs1057910)] and the blood pressure response to standardized amounts of salt (20 mmol per day vs. 200 mmol per day) in 309 young healthy normotensive white men. The main finding is that CYP2C9 Ã 3 carriers had lower plasma renin activity (PRA) than noncarriers, both under low and high dietary salt intakes [10].…”

“…The main finding is that CYP2C9 Ã 3 carriers had lower plasma renin activity (PRA) than noncarriers, both under low and high dietary salt intakes [10]. Bolbrinker et al [10] found no association of the studied CYP2C9 variants with the dichotomous salt-sensitivity phenotype or with the continuous blood pressure levels under low and high salt intakes. What does this mean?…”

“…First, variants of this gene have been associated with RAAS activity in humans [10,20]. Second, CYP2C9 Ã 3 has been associated with human hypertension, although only in women [21].…”