Atrial natriuretic peptide polymorphisms, hydrochlorothiazide and urinary potassium excretion

Abstract

Treatment outcome with the thiazide diuretic chlortalidone was partially associated with the two atrial natriuretic peptide (ANP) precursor gene (NPPA) polymorphisms Val32Met and Ter152Arg in the ALLHAT study. In our study with 25 and 100 mg hydrochlorothiazide in 103 normotensive volunteers the mean 24 h urinary potassium excretion was 3.6±0.1 and 3.9±0.1 g in only wild-type allele carriers with 25 and 100 mg hydrochlorothiazide. The potassium excretion was 0.5±0.2 and 0.6±0.2 g higher per arginine152 allele (p=0.004) and 1.1±0.5 and 1.0±0.5 g higher per methionine32 allele (p=0.016). No significant association was observed with volume, sodium, chloride or calcium excretion, with any electrolyte excretion on placebo days or with serum electrolyte concentration measures. In conclusion, proneness to hypokalemia may corrupt thiazide treatment outcome in carriers of such low functional ANP alleles. Potassium excretion and serum concentrations should thus be given increased attention in future research.