title: The dopamine receptor D2 genotype is associated with hyperprolactinemia.
abstract: OBJECTIVE
  To evaluate patients with hyperprolactinemia for the presence of dopamine receptor D2 polymorphisms.
  
  
  METHODS
  Case-control study.
  
  
  METHODS
  Academic research environment.
  
  
  METHODS
  Women and men with pathologic hyperprolactinemia and healthy controls.
  
  
  METHODS
  DNA extraction of peripheral blood, polymerase chain reaction, single-strand conformation polymorphism, DNA sequencing, and restriction digest.
  
  
  METHODS
  Two polymorphisms in exon 7 of the dopamine receptor D2 (DRD2) gene. Polymorphism 1 involves nucleotide 3420 (C to T, 313 His), and polymorphism 2 involves nucleotide 3438 (C to T, 319 Pro).
  
  
  RESULTS
  The frequency of DRD2 polymorphism 1 alleles was increased in subjects with hyperprolactinemia. Analysis of the DRD2 genotypes demonstrates an odds ratio of 6.77 (2.39, 19.14; 95% confidence interval) for the polymorphism 1 homozygous state in hyperprolactinemia.
  
  
  CONCLUSIONS
  A genetic predisposition to hyperprolactinemia is suggested by an excess homozygosity for polymorphism 1 in exon 7 of the DRD2 gene. Previous studies of lactotrophs from prolactinomas have found normal DRD2 receptors but differing isoform density. Homozygosity of polymorphism 1 may influence the distribution of the DRD2 isoforms on the lactotroph. Other potential mechanisms include an association with a molecular defect in a postreceptor signaling mechanism, such as a somatic inactivating mutation in a G1 protein, which could result in autonomous function of the lactotroph. Mutations could also result in different receptor-G protein interactions, such as a Gs instead of Gi, and result in autonomous lactotroph function.
authors.affiliation: Department of Obstetrics and Gynecology, University of South Dakota School of Medicine, Sioux Falls, South Dakota 57105, USA. kahansen@usd.edu
authors.forename: Keith A
authors.initials: KA
authors.lastname: Hansen
authors.forename: Yueyi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Robert
authors.initials: R
authors.lastname: Colver
authors.forename: Sandra P T
authors.initials: SP
authors.lastname: Tho
authors.forename: Leo
authors.initials: L
authors.lastname: Plouffe
authors.forename: Paul G
authors.initials: PG
authors.lastname: McDonough
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005838:Genotype; D006801:Humans; D006966:Hyperprolactinemia / Q000235:genetics*; D008297:Male; D016017:Odds Ratio; D012150:Polymorphism, Restriction Fragment Length; D017448:Receptors, Dopamine D2 / Q000235:genetics*
chemical_list: D017448:Receptors, Dopamine D2