Influence of Receptor Polymorphisms on the Response to alpha-Adrenergic Receptor Blockers in Pheochromocytoma Patients

Annika M A Berends*, Mathieu S Bolhuis, Ilja M Nolte, Edward Buitenwerf, Thera P Links, Henri J L M Timmers, Richard A Feelders, Elisabeth M W Eekhoff, Eleonora P M Corssmit, Peter H Bisschop, Harm R Haak, Ron H N van Schaik, Samira El Bouazzaoui, Bob Wilffert, Michiel N Kerstens

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

9 Downloads (Pure)

Abstract

Background: Presurgical treatment with an α-adrenergic receptor blocker is recommended to antagonize the catecholamine-induced α-adrenergic receptor mediated vasoconstriction in patients with pheochromocytoma or sympathetic paraganglioma (PPGL). There is, however, a considerable interindividual variation in the dose-response relationship regarding the magnitude of blood pressure reduction or the occurrence of side effects. We hypothesized that genetically determined differences in α-adrenergic receptor activity contribute to this variability in dose-response relationship.

Methods: Thirty-one single-nucleotide polymorphisms (SNPs) of the α1A, α1B, α1D adrenoreceptor (ADRA1A, ADRA1B, ADRA1D) and α2A, α2B adrenoreceptor (ADRA2A, ADRA2B) genes were genotyped in a group of 116 participants of the PRESCRIPT study. Haplotypes were constructed after determining linkage disequilibrium blocks.

Results: The ADRA1B SNP rs10515807 and the ADRA2A SNPs rs553668/rs521674 were associated with higher dosages of α-adrenergic receptor blocker (p < 0.05) and with a higher occurrence of side effects (rs10515807) (p = 0.005). Similar associations were found for haplotype block 6, which is predominantly defined by rs10515807.

Conclusions: This study suggests that genetic variability of α-adrenergic receptor genes might be associated with the clinically observed variation in beneficial and adverse therapeutic drug responses to α-adrenergic receptor blockers. Further studies in larger cohorts are needed to confirm our observations.

Original languageEnglish
Article number896
Number of pages15
JournalBiomedicines
Volume10
Issue number4
DOIs
Publication statusPublished - 13-Apr-2022

Keywords

  • pheochromocytoma
  • paraganglioma
  • single nucleotide polymorphism
  • adrenergic receptor
  • alpha-adrenergic receptor blocker
  • pharmacogenetics
  • personalized medicine
  • GENOME-WIDE ASSOCIATION
  • GENETIC-VARIATION
  • BLOOD-PRESSURE
  • ALPHA(1B)-ADRENERGIC RECEPTOR
  • ALPHA(2B)-ADRENERGIC RECEPTOR
  • ALPHA-1-ADRENERGIC RECEPTOR
  • FASTING GLUCOSE
  • ADRA2A
  • VARIANTS
  • HYPERTENSION

Cite this