Influence of Receptor Polymorphisms on the Response to α-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
Affiliations
Annika M. A. Berends
Department of Endocrinology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
Mathieu S. Bolhuis
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands
Ilja M. Nolte
Department of Epidemiology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands
Edward Buitenwerf
Department of Endocrinology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
Thera P. Links
Department of Endocrinology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
Henri J. L. M. Timmers
Department of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands
Richard A. Feelders
Department of Endocrinology, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands
Elisabeth M. W. Eekhoff
Department of Internal Medicine Section Endocrinology, Amsterdam University Medical Centers Location VUmc, 1117 HV Amsterdam, The Netherlands
Eleonora P. M. Corssmit
Department of Internal Medicine, Division of Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands
Peter H. Bisschop
Department of Internal Medicine Section Endocrinology, Amsterdam University Medical Centers Location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands
Harm R. Haak
Department of Internal Medicine, Máxima Medical Center, 5504 DB Eindhoven/Veldhoven, The Netherlands
Ron H. N. van Schaik
Department of Clinical Chemistry, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands
Samira el Bouazzaoui
Department of Clinical Chemistry, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands
Bob Wilffert
Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands
Michiel N. Kerstens
Department of Endocrinology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands
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 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.
