Influence of Receptor Polymorphisms on the Response to α-Adrenergic Receptor Blockers in Pheochromocytoma Patients
<b>Background:</b> 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 i...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-04-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/10/4/896 |
| _version_ | 1797436742523944960 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Annika M. A. Berends |
| collection | DOAJ |
| description | <b>Background:</b> 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. <b>Methods:</b> Thirty-one single-nucleotide polymorphisms (SNPs) of the α1A, α1B, α1D adrenoreceptor (<i>ADRA1A</i>, <i>ADRA1B</i>, <i>ADRA1D</i>) and α2A, α2B adrenoreceptor (<i>ADRA2A, ADRA2B</i>) genes were genotyped in a group of 116 participants of the PRESCRIPT study. Haplotypes were constructed after determining linkage disequilibrium blocks. <b>Results:</b> The <i>ADRA1B</i> SNP rs10515807 and the <i>ADRA2A</i> SNPs rs553668/rs521674 were associated with higher dosages of α-adrenergic receptor blocker (<i>p</i> < 0.05) and with a higher occurrence of side effects (rs10515807) (<i>p</i> = 0.005). Similar associations were found for haplotype block 6, which is predominantly defined by rs10515807. <b>Conclusions:</b> 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. |
| first_indexed | 2024-03-09T11:06:58Z |
| format | Article |
| id | doaj.art-47388fe947114605b5393398298c233c |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T11:06:58Z |
| publishDate | 2022-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-47388fe947114605b5393398298c233c2023-12-01T00:55:02ZengMDPI AGBiomedicines2227-90592022-04-0110489610.3390/biomedicines10040896Influence of Receptor Polymorphisms on the Response to α-Adrenergic Receptor Blockers in Pheochromocytoma PatientsAnnika M. A. Berends0Mathieu S. Bolhuis1Ilja M. Nolte2Edward Buitenwerf3Thera P. Links4Henri J. L. M. Timmers5Richard A. Feelders6Elisabeth M. W. Eekhoff7Eleonora P. M. Corssmit8Peter H. Bisschop9Harm R. Haak10Ron H. N. van Schaik11Samira el Bouazzaoui12Bob Wilffert13Michiel N. Kerstens14Department of Endocrinology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The NetherlandsDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Epidemiology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Endocrinology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The NetherlandsDepartment of Endocrinology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The NetherlandsDepartment of Internal Medicine, Radboud University Medical Center, 6525 GA Nijmegen, The NetherlandsDepartment of Endocrinology, Erasmus University Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Internal Medicine Section Endocrinology, Amsterdam University Medical Centers Location VUmc, 1117 HV Amsterdam, The NetherlandsDepartment of Internal Medicine, Division of Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, The NetherlandsDepartment of Internal Medicine Section Endocrinology, Amsterdam University Medical Centers Location AMC, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsDepartment of Internal Medicine, Máxima Medical Center, 5504 DB Eindhoven/Veldhoven, The NetherlandsDepartment of Clinical Chemistry, Erasmus University Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Clinical Chemistry, Erasmus University Medical Center, 3015 GD Rotterdam, The NetherlandsDepartment of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Center Groningen, 9713 GZ Groningen, The NetherlandsDepartment of Endocrinology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands<b>Background:</b> 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. <b>Methods:</b> Thirty-one single-nucleotide polymorphisms (SNPs) of the α1A, α1B, α1D adrenoreceptor (<i>ADRA1A</i>, <i>ADRA1B</i>, <i>ADRA1D</i>) and α2A, α2B adrenoreceptor (<i>ADRA2A, ADRA2B</i>) genes were genotyped in a group of 116 participants of the PRESCRIPT study. Haplotypes were constructed after determining linkage disequilibrium blocks. <b>Results:</b> The <i>ADRA1B</i> SNP rs10515807 and the <i>ADRA2A</i> SNPs rs553668/rs521674 were associated with higher dosages of α-adrenergic receptor blocker (<i>p</i> < 0.05) and with a higher occurrence of side effects (rs10515807) (<i>p</i> = 0.005). Similar associations were found for haplotype block 6, which is predominantly defined by rs10515807. <b>Conclusions:</b> 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.https://www.mdpi.com/2227-9059/10/4/896pheochromocytomaparagangliomasingle nucleotide polymorphismadrenergic receptoralpha-adrenergic receptor blockerpharmacogenetics |
| spellingShingle | 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 Influence of Receptor Polymorphisms on the Response to α-Adrenergic Receptor Blockers in Pheochromocytoma Patients Biomedicines pheochromocytoma paraganglioma single nucleotide polymorphism adrenergic receptor alpha-adrenergic receptor blocker pharmacogenetics |
| title | Influence of Receptor Polymorphisms on the Response to α-Adrenergic Receptor Blockers in Pheochromocytoma Patients |
| title_full | Influence of Receptor Polymorphisms on the Response to α-Adrenergic Receptor Blockers in Pheochromocytoma Patients |
| title_fullStr | Influence of Receptor Polymorphisms on the Response to α-Adrenergic Receptor Blockers in Pheochromocytoma Patients |
| title_full_unstemmed | Influence of Receptor Polymorphisms on the Response to α-Adrenergic Receptor Blockers in Pheochromocytoma Patients |
| title_short | Influence of Receptor Polymorphisms on the Response to α-Adrenergic Receptor Blockers in Pheochromocytoma Patients |
| title_sort | influence of receptor polymorphisms on the response to α adrenergic receptor blockers in pheochromocytoma patients |
| topic | pheochromocytoma paraganglioma single nucleotide polymorphism adrenergic receptor alpha-adrenergic receptor blocker pharmacogenetics |
| url | https://www.mdpi.com/2227-9059/10/4/896 |
| work_keys_str_mv | AT annikamaberends influenceofreceptorpolymorphismsontheresponsetoaadrenergicreceptorblockersinpheochromocytomapatients AT mathieusbolhuis influenceofreceptorpolymorphismsontheresponsetoaadrenergicreceptorblockersinpheochromocytomapatients AT iljamnolte influenceofreceptorpolymorphismsontheresponsetoaadrenergicreceptorblockersinpheochromocytomapatients AT edwardbuitenwerf influenceofreceptorpolymorphismsontheresponsetoaadrenergicreceptorblockersinpheochromocytomapatients AT theraplinks influenceofreceptorpolymorphismsontheresponsetoaadrenergicreceptorblockersinpheochromocytomapatients AT henrijlmtimmers influenceofreceptorpolymorphismsontheresponsetoaadrenergicreceptorblockersinpheochromocytomapatients AT richardafeelders influenceofreceptorpolymorphismsontheresponsetoaadrenergicreceptorblockersinpheochromocytomapatients AT elisabethmweekhoff influenceofreceptorpolymorphismsontheresponsetoaadrenergicreceptorblockersinpheochromocytomapatients AT eleonorapmcorssmit influenceofreceptorpolymorphismsontheresponsetoaadrenergicreceptorblockersinpheochromocytomapatients AT peterhbisschop influenceofreceptorpolymorphismsontheresponsetoaadrenergicreceptorblockersinpheochromocytomapatients AT harmrhaak influenceofreceptorpolymorphismsontheresponsetoaadrenergicreceptorblockersinpheochromocytomapatients AT ronhnvanschaik influenceofreceptorpolymorphismsontheresponsetoaadrenergicreceptorblockersinpheochromocytomapatients AT samiraelbouazzaoui influenceofreceptorpolymorphismsontheresponsetoaadrenergicreceptorblockersinpheochromocytomapatients AT bobwilffert influenceofreceptorpolymorphismsontheresponsetoaadrenergicreceptorblockersinpheochromocytomapatients AT michielnkerstens influenceofreceptorpolymorphismsontheresponsetoaadrenergicreceptorblockersinpheochromocytomapatients |