title: Cabergoline and prolactinomas: lack of association between DRD2 polymorphisms and response to treatment.
abstract: BACKGROUND
  About 80% of prolactinomas respond to dopamine agonists (DA) with hormonal normalization and tumor shrinkage. Mechanisms of DA resistance include reduction of dopamine receptor subtype 2 (DRD2) expression, short and long isoform ratio and post-receptor mechanisms. It was suggested that polymorphisms in the gene encoding dopamine receptor subtype 2 gene (DRD2) could be associated with variable effectiveness of cabergoline (CAB).
  
  
  OBJECTIVE
  To assess the influence of DRD2 polymorphisms in responsiveness of CAB treatment in patients with prolactinoma.
  
  
  METHODS
  Cross-sectional retrospective case-control study analyzing the frequency of five DRD2 polymorphisms in 148 patients with prolactinoma and 349 healthy subjects. The association of genetic variants and clinical characteristics with CAB responsiveness was performed in 118 patients (mean age at diagnosis 29 years; range 11-61 years) with hormonal evaluation. Patients with prolactin (PRL) normalization were considered as responders.
  
  
  RESULTS
  No association in genotypes and allele proportions was found comparing patients and controls. On pharmacogenetic study, 118 patients on CAB were included and 20% were non-responders. No association was found between clinical characteristics (gender, age, PRL level and tumor size at diagnosis) and polymorphisms of DRD2 with CAB responsiveness. Otherwise, there was association between polymorphisms rs1076560 (allele A) and rs1800497 (allele T) and the presence of macroadenomas.
  
  
  CONCLUSIONS
  No correlation was found between DRD2 polymorphisms and CAB responsiveness in patients with prolactinoma. More data are necessary in order to assess the influence of DRD2 genotyping on DA treatment response.
authors.affiliation: Neuroendocrine Unit, Division of Endocrinology and Metabolism, Hospital das Clínicas & Laboratory of Cellular and Molecular Endocrinology LIM-25, University of São Paulo Medical School, São Paulo, Brazil. cbformiga@gmail.com.
authors.forename: Cbf
authors.initials: C
authors.lastname: Bueno
authors.affiliation: Neuroendocrine Unit, Division of Endocrinology and Metabolism, Hospital das Clínicas & Laboratory of Cellular and Molecular Endocrinology LIM-25, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: E B
authors.initials: EB
authors.lastname: Trarbach
authors.affiliation: Neuroendocrine Unit, Division of Endocrinology and Metabolism, Hospital das Clínicas & Laboratory of Cellular and Molecular Endocrinology LIM-25, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: M D
authors.initials: MD
authors.lastname: Bronstein
authors.affiliation: Neuroendocrine Unit, Division of Endocrinology and Metabolism, Hospital das Clínicas & Laboratory of Cellular and Molecular Endocrinology LIM-25, University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: A
authors.initials: A
authors.lastname: Glezer
mesh_terms: D000293:Adolescent; D000328:Adult; D000077465:Cabergoline; D016022:Case-Control Studies; D002648:Child; D003430:Cross-Sectional Studies; D018491:Dopamine Agonists / Q000627:therapeutic use*; D004873:Ergolines / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D015175:Prolactinoma / Q000188:drug therapy* / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D018491:Dopamine Agonists; D004873:Ergolines; D017448:Receptors, Dopamine D2; D000077465:Cabergoline
keywords: Cabergoline; DRD2; Dopamine agonist; Polymorphism; Prolactinoma