Dopamine D2 receptor gene polymorphisms and response to cabergoline therapy in patients with prolactin-secreting pituitary adenomas.
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.
Filopanti
M
M
Department of Medical Sciences, University of Milan, Endocrine and Diabetes Unit Fondazione Ospedale Maggiore IRCCS, Milan, Italy.
Barbieri
A M
AM
Angioni
A R
AR
Colao
A
A
Gasco
V
V
Grottoli
S
S
Peri
A
A
Baglioni
S
S
Fustini
M F
MF
Pigliaru
F
F
Monte
P D
PD
Borretta
G
G
Ambrosi
B
B
Jaffrain-Rea
M L
ML
Gasperi
M
M
Brogioni
S
S
Cannavò
S
S
Mantovani
G
G
Beck-Peccoz
P
P
Lania
A
A
Spada
A
A
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
D018491:Dopamine Agonists; D004873:Ergolines; D017448:Receptors, Dopamine D2; D011388:Prolactin; D000077465:Cabergoline