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

M. Filopanti, A. M. Barbieri, A. R. Angioni, A. Colao, V. Gasco, S. Grottoli, A. Peri, S. Baglioni, M. F. Fustini, F. Pigliaru, P. D. Monte, G. Borretta, B. Ambrosi, M. L. Jaffrain-Rea, M. Gasperi, S. Brogioni, S. Cannavò, G. Mantovani, P. Beck-Peccoz, A. LaniaA. Spada

Research output: Contribution to journalArticle

Abstract

Dopamine-agonist cabergoline (CB) reduces prolactin (PRL) secretion and tumor size in 80% of patients with prolactin-secreting adenomas (PRL-omas) by binding type 2 dopamine receptor (DRD2). The mechanisms responsible for resistance to CB remain largely unknown. To assess the association of DRD2 with sensitivity to CB, TaqI-A1/A2, TaqI-B1/B2, HphI-G/T and NcoI-C/T genotypes were determined in a cross-sectional retrospective study, including 203 patients with PRL-oma. DRD2 alleles frequencies did not differ between patients and 212 healthy subjects. Conversely, NcoI-T allele frequency was higher in resistant rather than responsive patients, considering both PRL normalization (56.6 vs 45.3%, P=0.038) and tumor shrinkage (70.4 vs 41.4%, P=0.006). Finally, [TaqI A1-/TaqI B1-/HphI T-/NcoI T-] haplotype was found in 34.5% of patients normalizing PRL with ≤3 mg/week of CB vs 11.3% of resistants (P=0.021). In conclusion, resistance to CB was associated with DRD2 NcoI-T+ allele, consistent with evidence suggesting that this variant may lead to reduction and instability of DRD2 mRNA or protein.

Original languageEnglish
Pages (from-to)357-363
Number of pages7
JournalPharmacogenomics Journal
Volume8
Issue number5
DOIs
Publication statusPublished - 2008

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ASJC Scopus subject areas

  • Pharmacology
  • Molecular Medicine
  • Genetics
  • Medicine(all)

Cite this

Filopanti, M., Barbieri, A. M., Angioni, A. R., Colao, A., Gasco, V., Grottoli, S., Peri, A., Baglioni, S., Fustini, M. F., Pigliaru, F., Monte, P. D., Borretta, G., Ambrosi, B., Jaffrain-Rea, M. L., Gasperi, M., Brogioni, S., Cannavò, S., Mantovani, G., Beck-Peccoz, P., ... Spada, A. (2008). Dopamine D2 receptor gene polymorphisms and response to cabergoline therapy in patients with prolactin-secreting pituitary adenomas. Pharmacogenomics Journal, 8(5), 357-363. https://doi.org/10.1038/tpj.2008.1