Influence of Receptor Polymorphisms on the Response to α-Adrenergic Receptor Blockers in Pheochromocytoma Patients

被引:0
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作者
Berends, Annika M. A. [1 ]
Bolhuis, Mathieu S. [2 ]
Nolte, Ilja M. [3 ]
Buitenwerf, Edward [1 ]
Links, Thera P. [1 ]
Timmers, Henri J. L. M. [4 ]
Feelders, Richard A. [5 ]
Eekhoff, Elisabeth M. W. [6 ]
Corssmit, Eleonora P. M. [7 ]
Bisschop, Peter H. [8 ]
Haak, Harm R. [9 ,10 ,11 ]
van Schaik, Ron H. N. [12 ]
El Bouazzaoui, Samira [12 ]
Wilffert, Bob [2 ,13 ]
Kerstens, Michiel N. [1 ]
机构
[1] Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, Hanzepl 1, NL-9713 GZ Groningen, Netherlands
[2] Univ Groningen, Univ Med Ctr Groningen, Dept Clin Pharm & Pharmacol, NL-9713 GZ Groningen, Netherlands
[3] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-9713 GZ Groningen, Netherlands
[4] Radboud Univ Nijmegen Med Ctr, Dept Internal Med, NL-6525 GA Nijmegen, Netherlands
[5] Erasmus MC, Dept Endocrinol, NL-3015 GD Rotterdam, Netherlands
[6] Amsterdam Univ Med Ctr Locat VUmc, Dept Internal Med, Sect Endocrinol, NL-1117 HV Amsterdam, Netherlands
[7] Leiden Univ Med Ctr, Dept Internal Med, Div Endocrinol, NL-2333 ZA Leiden, Netherlands
[8] Univ Amsterdam, Amsterdam Univ Med Ctr Locat AMC, Dept Internal Med, Sect Endocrinol, NL-1105 AZ Amsterdam, Netherlands
[9] Maxima Med Ctr, Dept Internal Med, NL-5504 DB Eindhoven, Netherlands
[10] Maastricht Univ, CAPHRI Sch Publ Hlth & Primary Care Ageing & Long, NL-6229 HX Maastricht, Netherlands
[11] Maastricht Univ Med Ctr, Dept Internal Med, Div Gen Internal Med, NL-6229 HX Maastricht, Netherlands
[12] Erasmus MC, Dept Clin Chem, NL-3015 GD Rotterdam, Netherlands
[13] Univ Groningen, Groningen Res Inst Pharm, Dept Pharmacotherapy Epidemiol & Econ, NL-9713 GZ Groningen, Netherlands
关键词
pheochromocytoma; paraganglioma; single nucleotide polymorphism; adrenergic receptor; alpha-adrenergic receptor blocker; pharmacogenetics; personalized medicine; GENOME-WIDE ASSOCIATION; GENETIC-VARIATION; BLOOD-PRESSURE; ALPHA(1B)-ADRENERGIC RECEPTOR; ALPHA(2B)-ADRENERGIC RECEPTOR; ALPHA-1-ADRENERGIC RECEPTOR; FASTING GLUCOSE; ADRA2A; VARIANTS; HYPERTENSION;
D O I
10.3390/biomedicines10040896
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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/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.
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页数:15
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