title: Dopamine D2 receptor gene polymorphisms and response to cabergoline therapy in patients with prolactin-secreting pituitary adenomas.
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 < or =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.
authors.affiliation: Department of Medical Sciences, University of Milan, Endocrine and Diabetes Unit Fondazione Ospedale Maggiore IRCCS, Milan, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Filopanti
authors.forename: A M
authors.initials: AM
authors.lastname: Barbieri
authors.forename: A R
authors.initials: AR
authors.lastname: Angioni
authors.forename: A
authors.initials: A
authors.lastname: Colao
authors.forename: V
authors.initials: V
authors.lastname: Gasco
authors.forename: S
authors.initials: S
authors.lastname: Grottoli
authors.forename: A
authors.initials: A
authors.lastname: Peri
authors.forename: S
authors.initials: S
authors.lastname: Baglioni
authors.forename: M F
authors.initials: MF
authors.lastname: Fustini
authors.forename: F
authors.initials: F
authors.lastname: Pigliaru
authors.forename: P D
authors.initials: PD
authors.lastname: Monte
authors.forename: G
authors.initials: G
authors.lastname: Borretta
authors.forename: B
authors.initials: B
authors.lastname: Ambrosi
authors.forename: M L
authors.initials: ML
authors.lastname: Jaffrain-Rea
authors.forename: M
authors.initials: M
authors.lastname: Gasperi
authors.forename: S
authors.initials: S
authors.lastname: Brogioni
authors.forename: S
authors.initials: S
authors.lastname: Cannavò
authors.forename: G
authors.initials: G
authors.lastname: Mantovani
authors.forename: P
authors.initials: P
authors.lastname: Beck-Peccoz
authors.forename: A
authors.initials: A
authors.lastname: Lania
authors.forename: A
authors.initials: A
authors.lastname: Spada
mesh_terms: D000236:Adenoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000483:Alleles; D000077465:Cabergoline; D003430:Cross-Sectional Studies; D018491:Dopamine Agonists / Q000627:therapeutic use*; D004873:Ergolines / Q000627:therapeutic use*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic; D011388:Prolactin / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D018491:Dopamine Agonists; D004873:Ergolines; D017448:Receptors, Dopamine D2; D011388:Prolactin; D000077465:Cabergoline