TY - JOUR
T1 - Influence of Receptor Polymorphisms on the Response to α-Adrenergic Receptor Blockers in Pheochromocytoma Patients
AU - Berends, Annika M. A.
AU - Bolhuis, Mathieu S.
AU - Nolte, Ilja M.
AU - Buitenwerf, Edward
AU - Links, Thera P.
AU - Timmers, Henri J. L. M.
AU - Feelders, Richard A.
AU - Eekhoff, Elisabeth M. W.
AU - Corssmit, Eleonora P. M.
AU - Haak, Harm R.
AU - van Schaik, Ron H. N.
AU - el Bouazzaoui, Samira
AU - Wilffert, Bob
AU - Kerstens, Michiel N.
AU - Bisschop, Peter H.
N1 - Funding Information: Several authors of this publication are members of the European Reference Network on rare endocrine conditions?Project ID No 739527. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/4/1
Y1 - 2022/4/1
N2 - 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.
AB - 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.
KW - adrenergic receptor
KW - alpha-adrenergic receptor blocker
KW - paraganglioma
KW - personalized medicine
KW - pharmacogenetics
KW - pheochromocytoma
KW - single nucleotide polymorphism
UR - http://www.scopus.com/inward/record.url?scp=85129160532&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/biomedicines10040896
DO - https://doi.org/10.3390/biomedicines10040896
M3 - Article
C2 - 35453646
SN - 2227-9059
VL - 10
JO - Biomedicines
JF - Biomedicines
IS - 4
M1 - 896
ER -