Influence of Receptor Polymorphisms on the Response to α-Adrenergic Receptor Blockers in Pheochromocytoma Patients.
adrenergic receptor
alpha-adrenergic receptor blocker
paraganglioma
personalized medicine
pharmacogenetics
pheochromocytoma
single nucleotide polymorphism
Journal
Biomedicines
ISSN: 2227-9059
Titre abrégé: Biomedicines
Pays: Switzerland
ID NLM: 101691304
Informations de publication
Date de publication:
13 Apr 2022
13 Apr 2022
Historique:
received:
16
03
2022
revised:
06
04
2022
accepted:
08
04
2022
entrez:
23
4
2022
pubmed:
24
4
2022
medline:
24
4
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35453646
pii: biomedicines10040896
doi: 10.3390/biomedicines10040896
pmc: PMC9028965
pii:
doi:
Types de publication
Journal Article
Langues
eng
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