The dopamine receptor D2 genotype is associated with hyperprolactinemia

Fertil Steril. 2005 Sep;84(3):711-8. doi: 10.1016/j.fertnstert.2005.03.040.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Case-Control Studies
  • Chi-Square Distribution
  • Female
  • Genotype
  • Humans
  • Hyperprolactinemia / genetics*
  • Male
  • Odds Ratio
  • Polymorphism, Restriction Fragment Length
  • Receptors, Dopamine D2 / genetics*

Substances

  • Receptors, Dopamine D2