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

The Pharmacogenomics Journal volume 8, pages 357–363 (2008)Cite this article

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.

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Abbreviations

CB:

cabergoline

DRD2:

type 2 dopamine receptor

PRL:

prolactin

PRL-oma:

PRL-secreting pituitary adenoma

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Acknowledgements

This work was partially supported by FIRST, Fondazione Ospedale Maggiore IRCCS and Associazione Italiana per la Ricerca sul Cancro AIRC (Milan). We are grateful to Drs EP Noble and T Ritchie for advice concerning analysis of NcoI and HphI polymorphisms.

Author information

Authors and Affiliations

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

    M Filopanti, A M Barbieri, A R Angioni, G Mantovani, P Beck-Peccoz, A Lania & A Spada

  2. Department of Molecular and Clinical Endocrinology and Oncology, Federico II University of Naples, Naples, Italy

    A Colao

  3. Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Turin, Turin, Italy

    V Gasco & S Grottoli

  4. Department of Clinical Physiopathology, Endocrine Unit, Center for Research, Transfer and High Education DENOThe, University of Florence, Florence, Italy

    A Peri & S Baglioni

  5. Department of Medicine, Endocrinology Unit, Ospedale Bellaria, Bologna, Italy

    M F Fustini

  6. Department of Medical Sciences ‘M. Aresu’, Endocrinology, University of Cagliari, Cagliari, Italy

    F Pigliaru

  7. Unit of Endocrinology, Galliera Hospital, Genoa, Italy

    P D Monte

  8. Endocrinology Unit, Santa Croce Hospital, Cuneo, Italy

    G Borretta

  9. Department of Medical and Surgical Sciences, Endocrinology Unit, University of Milan, IRCCS Policlinico San Donato, Milan, Italy

    B Ambrosi

  10. Department of Experimental Medicine, University of L'Aquila and Neuromed IRCCS, Pozzilli, Italy

    M L Jaffrain-Rea

  11. Chair of Endocrinology, University of Molise, Campobasso, Italy

    M Gasperi

  12. Department of Endocrinology, University of Pisa, Pisa, Italy

    S Brogioni

  13. Department of Medicine and Pharmacology, University of Messina, Messina, Italy

    S Cannavò

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  1. M Filopanti
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  2. A M Barbieri
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  3. A R Angioni
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  7. A Peri
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  8. S Baglioni
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  12. G Borretta
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  14. M L Jaffrain-Rea
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  16. S Brogioni
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  17. S Cannavò
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  18. G Mantovani
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  19. P Beck-Peccoz
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  20. A Lania
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  21. A Spada
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Corresponding author

Correspondence to A Spada.

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None declared.

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Filopanti, M., Barbieri, A., Angioni, A. et al. Dopamine D2 receptor gene polymorphisms and response to cabergoline therapy in patients with prolactin-secreting pituitary adenomas. Pharmacogenomics J 8, 357–363 (2008). https://doi.org/10.1038/tpj.2008.1

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  • DOI: https://doi.org/10.1038/tpj.2008.1

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