Dopamine D2 receptor gene polymorphisms and response to cabergoline therapy in patients with prolactin-secreting pituitary adenomas
Articolo
Data di Pubblicazione:
2008
Citazione:
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. Lania, A. Spada. - In: PHARMACOGENOMICS JOURNAL. - ISSN 1470-269X. - 8:5(2008 Oct), pp. 357-363. [10.1038/tpj.2008.1]
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.
Tipologia IRIS:
01 - Articolo su periodico
Elenco autori:
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. Lania, A. Spada
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