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Cabergoline and prolactinomas: lack of association between DRD2 polymorphisms and response to treatment

Abstract

Background

About 80% of prolactinomas respond to dopamine agonists (DA) with hormonal normalization and tumor shrinkage. Mechanisms of DA resistance include reduction of dopamine receptor subtype 2 (DRD2) expression, short and long isoform ratio and post-receptor mechanisms. It was suggested that polymorphisms in the gene encoding dopamine receptor subtype 2 gene (DRD2) could be associated with variable effectiveness of cabergoline (CAB).

Objective

To assess the influence of DRD2 polymorphisms in responsiveness of CAB treatment in patients with prolactinoma.

Study design and patients

Cross-sectional retrospective case–control study analyzing the frequency of five DRD2 polymorphisms in 148 patients with prolactinoma and 349 healthy subjects. The association of genetic variants and clinical characteristics with CAB responsiveness was performed in 118 patients (mean age at diagnosis 29 years; range 11–61 years) with hormonal evaluation. Patients with prolactin (PRL) normalization were considered as responders.

Results

No association in genotypes and allele proportions was found comparing patients and controls. On pharmacogenetic study, 118 patients on CAB were included and 20% were non-responders. No association was found between clinical characteristics (gender, age, PRL level and tumor size at diagnosis) and polymorphisms of DRD2 with CAB responsiveness. Otherwise, there was association between polymorphisms rs1076560 (allele A) and rs1800497 (allele T) and the presence of macroadenomas.

Conclusion

No correlation was found between DRD2 polymorphisms and CAB responsiveness in patients with prolactinoma. More data are necessary in order to assess the influence of DRD2 genotyping on DA treatment response.

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Acknowledgements

This work was supported by institutional grant from CAPES (to C.B.F.B.); Grant 2011/19932-5 from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and Federico Foundation (to A.G.).

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Correspondence to CBF Bueno.

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Bueno, C., Trarbach, E., Bronstein, M. et al. Cabergoline and prolactinomas: lack of association between DRD2 polymorphisms and response to treatment. Pituitary 20, 295–300 (2017). https://doi.org/10.1007/s11102-016-0776-4

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  • DOI: https://doi.org/10.1007/s11102-016-0776-4

Keywords

  • Polymorphism
  • DRD2
  • Prolactinoma
  • Dopamine agonist
  • Cabergoline