The dopamine receptor D2 genotype is associated with hyperprolactinemia.
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.
Hansen
Keith A
KA
Department of Obstetrics and Gynecology, University of South Dakota School of Medicine, Sioux Falls, South Dakota 57105, USA. kahansen@usd.edu
Zhang
Yueyi
Y
Colver
Robert
R
Tho
Sandra P T
SP
Plouffe
Leo
L
McDonough
Paul G
PG
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*
D017448:Receptors, Dopamine D2