Pharmacogenetics of Thiazide Diuretics: An Update on Inter-individual Variations

Abstract

Hypertension is a common disorder, representing a leading cause of cardiovascular mortality worldwide. Thiazide diuretics, mainly hydrochlorothiazide, are among the most widely prescribed antihypertensive agents. Treatment with thiazide diuretics has reported large inter-individual differences in blood pressure (BP) responses, assuring the great need for pharmacogenetic studies. Over the past decade, significant advances have been made in the field of cardiovascular pharmacogenomics. This narrative review summarizes the current state of knowledge regarding the pharmacogenetic effects of thiazide diuretics on BP-lowering efficacy and safety. After performing a MEDLINE search, relevant literature was collected until September 2015, thus several inter-individual variations were highlighted. We provided clarity for single-nucleotide polymorphisms of genes that have been extensively studied relative to thiazide diuretics. Genetic polymorphisms in many candidate genes like alpha-adducin 1, G protein β3-subunit, subunit of sodium channel, and others were suggested to affect BP response and toxicity to thiazide diuretic therapy. Many inter-individual variations presented differences in efficacy and adverse events between different ethnicities and genders necessitating the tailoring of thiazide diuretic therapy and the targeting of new sites of action.

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Correspondence to Safaa Hammoud.

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Endorsed by Asser Ghoneim.

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Hammoud, S., Ghoneim, A. Pharmacogenetics of Thiazide Diuretics: An Update on Inter-individual Variations. Springer Science Reviews 4, 15–23 (2016). https://doi.org/10.1007/s40362-016-0038-x

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Keywords

  • Thiazide diuretics
  • Pharmacogenetics
  • Hypertension
  • Single-nucleotide polymorphisms
  • Antihypertensive efficacy and safety