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Berends, A.M.A.; Bolhuis, M.S.; Nolte, I.M.; Buitenwerf, E.; Links, T.P.; Timmers, H.J.L.M.; ... ; Kerstens, M.N. (2022)

Influence of receptor polymorphisms on the response to alpha-adrenergic receptor blockers in pheochromocytoma patients

Article / Letter to editor
Background: Presurgical treatment with an alpha-adrenergic receptor blocker is recommended to antagonize the catecholamine-induced alpha-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 alpha-adrenergic receptor activity contribute to this variability in dose-response relationship. Methods: Thirty-one single-nucleotide polymorphisms (SNPs) of the alpha 1A, alpha 1B, alpha 1D adrenoreceptor (ADRA1A, ADRA1B, ADRA1D) and alpha 2A, alpha 2B 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...Show moreBackground: Presurgical treatment with an alpha-adrenergic receptor blocker is recommended to antagonize the catecholamine-induced alpha-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 alpha-adrenergic receptor activity contribute to this variability in dose-response relationship. Methods: Thirty-one single-nucleotide polymorphisms (SNPs) of the alpha 1A, alpha 1B, alpha 1D adrenoreceptor (ADRA1A, ADRA1B, ADRA1D) and alpha 2A, alpha 2B 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 alpha-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 alpha-adrenergic receptor genes might be associated with the clinically observed variation in beneficial and adverse therapeutic drug responses to alpha-adrenergic receptor blockers. Further studies in larger cohorts are needed to confirm our observations.Show less
pheochromocytoma
paraganglioma
single nucleotide polymorphism
adrenergic receptor
alpha-adrenergic receptor blocker
pharmacogenetics
personalized medicine
All authors
Berends, A.M.A.; Bolhuis, M.S.; Nolte, I.M.; Buitenwerf, E.; Links, T.P.; Timmers, H.J.L.M.; Feelders, R.A.; Eekhoff, E.M.W.; Corssmit, E.P.M.; Bisschop, P.H.; Haak, H.R.; Schaik, R.H.N. van; Bouazzaoui, S. el; Wilffert, B.; Kerstens, M.N.
Date
2022-04-01
Journal
Biomedicines
Volume
10
Issue
4
DOI
doi:10.3390/biomedicines10040896