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Dopamine D2 receptor gene polymorphisms and response to cabergoline therapy in patients with prolactin-secreting

M Filopanti1, A M Barbieri, A R Angioni

  • 1Department of Medical Sciences, University of Milan, Endocrine and Diabetes Unit Fondazione Ospedale Maggiore IRCCS, Milan, Italy.

The Pharmacogenomics Journal
|March 12, 2008
PubMed

Insights

Resistance to cabergoline (CB), a dopamine agonist, in prolactinomas may be linked to the DRD2 NcoI-T allele. This genetic variant might affect dopamine receptor type 2 (DRD2) expression, influencing treatment effectiveness.

Area of Science:

  • Endocrinology
  • Genetics
  • Pharmacology

Background:

  • Cabergoline (CB) effectively treats prolactinomas by targeting dopamine receptor type 2 (DRD2).
  • Mechanisms underlying resistance to cabergoline remain poorly understood.
  • Prolactinomas are tumors that secrete prolactin (PRL), often leading to hormonal imbalances.

Purpose of the Study:

  • To investigate the association between dopamine receptor type 2 (DRD2) genotypes and sensitivity to cabergoline (CB) in patients with prolactinomas.
  • To identify genetic markers that may predict resistance or responsiveness to cabergoline treatment.

Main Methods:

  • A cross-sectional retrospective study involving 203 patients with prolactinomas.
  • Genotyping for DRD2 polymorphisms: TaqI-A1/A2, TaqI-B1/B2, HphI-G/T, and NcoI-C/T.
  • Comparison of allele frequencies between responsive and resistant patient groups and healthy subjects.

Main Results:

  • No significant difference in DRD2 allele frequencies was observed between patients and healthy controls.
  • The NcoI-T allele frequency was significantly higher in patients resistant to CB compared to responsive patients (P=0.038 for PRL normalization; P=0.006 for tumor shrinkage).
  • A specific haplotype [TaqI A1-/TaqI B1-/HphI T-/NcoI T-] was more prevalent in patients achieving PRL normalization with lower CB doses (P=0.021).

Conclusions:

  • Resistance to cabergoline in prolactinoma patients is associated with the DRD2 NcoI-T allele.
  • This DRD2 variant may contribute to reduced or unstable DRD2 mRNA or protein levels, impacting treatment efficacy.
  • Genetic profiling of DRD2 may offer insights into predicting cabergoline response in prolactinoma management.

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