The dopamine receptor D2 genotype is associated with hyperprolactinemia

Keith A. Hansen, Yueyi Zhang, Robert Colver, Sandra P.T. Tho, Leo Plouffe, Paul G. McDonough

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Objective: To evaluate patients with hyperprolactinemia for the presence of dopamine receptor D2 polymorphisms. Design: Case-control study. Setting: Academic research environment. Patient(s): Women and men with pathologic hyperprolactinemia and healthy controls. Intervention(s): DNA extraction of peripheral blood, polymerase chain reaction, single-strand conformation polymorphism, DNA sequencing, and restriction digest. Main Outcome Measure(s): 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). Result(s): 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. Conclusion(s): 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.

Original languageEnglish (US)
Pages (from-to)711-718
Number of pages8
JournalFertility and sterility
Volume84
Issue number3
DOIs
StatePublished - Sep 1 2005

Keywords

  • Dopamine receptor D
  • Hyperprolactinemia
  • Pituitary adenomas

ASJC Scopus subject areas

  • Reproductive Medicine
  • Obstetrics and Gynecology

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    Hansen, K. A., Zhang, Y., Colver, R., Tho, S. P. T., Plouffe, L., & McDonough, P. G. (2005). The dopamine receptor D2 genotype is associated with hyperprolactinemia. Fertility and sterility, 84(3), 711-718. https://doi.org/10.1016/j.fertnstert.2005.03.040