OP.6D.05] INFLUENCE OF MULTIDRUG RESISTANCE P-GLYCOPROTEIN GENE POLYMORPHISM OR INHBITION ON PLASMA ALDOSTERONE CONCENTRATION IN HEALTHY SUBJECTS

Abstract

Objective: The multidrug resistance P-glycoprotein (P-gp) has been shown to contribute to the secretion of aldosterone by human adrenal cells in vitro. To address the clinical relevance of this finding, we studied the impact of a loss of function P-gp polymorphism of ABCB1 gene and of clarithromycin, a P-gp inhibitor, on plasma aldosterone (PAC) and renin (PRC) concentrations in heathy subjects. Design and method: Three groups of 20 healthy normotensive male volunteers were selected on the basis of their ABCB1 genotype: CC non carriers, heterozygous CT and TT homozygous carriers of haplotype 2677–3435. PAC, PRC and urinary aldosterone excretionwere measured at 09:00 in semi-recumbent position and on ad libitum sodium diet at baseline and after 5-day treatment with the P-gp inhibitor, clarithromycin (200 MG bid). Results: Age, BMI, blood pressure, plasma Na and K concentrations, PAC and UAE (urinary adlosterone excretion) did not differ among the genotypes. There was a trend for an increase in PRC between CC, CT and TT subjects with a significantly higher PRC in TT than in CC subjects (mean difference: + 34% [95%CI%: 4–50%], p = 0.0295). PRC, PAC and UAE were not affected by clarithromycin in the CC group (p = 0.2746, 0.2860 and 0.2274, respectively), or in the CT and TT groups.Conclusions: The 2677–3435 P-gp haplotype and Pg-p inhibition were not associated with significant differences in aldosterone secretion in physiological conditions on a normal sodium intake in healthy subjects. The slightly higher PRC in homozygous carrier TT subjects than in non-carrier CC subjects may reflect a subtle impairment of aldosterone secretion. Whether this subtle abnormality on steady state may predict an impaired adaption of aldosterone secretion in pathophysiological conditions remains to be established.