The dopamine receptor D2 genotype is associated with hyperprolactinemia

• Published in: Fertility and sterility Vol. 84; no. 3; pp. 711 - 718
• Main Authors: HANSEN, Keith A, YUEYI ZHANG, COLVER, Robert, THO, Sandra P. T, PLOUFFE, Leo JR, MCDONOUGH, Paul G
• Format: Conference Proceeding Journal Article
• Language: English
• Published: New York, NY Elsevier Science 01.09.2005
• Subjects: Alleles; Biological and medical sciences; Case-Control Studies; Chi-Square Distribution; Endocrinopathies; Female; Genotype; Gynecology. Andrology. Obstetrics; Humans; Hyperprolactinemia - genetics; Hypothalamus. Hypophysis. Epiphysis (diseases); Male; Medical sciences; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Odds Ratio; Polymorphism, Restriction Fragment Length; Receptors, Dopamine D2 - genetics; Endocrinopathy; dopamine receptor D2; D2 Dopamine receptor; Fertility; Hyperprolactinemia; Pituitary diseases; pituitary adenomas; Genotype; Pituitary Adenoma
• ISSN: 0015-0282; 1556-5653
• DOI: 10.1016/j.fertnstert.2005.03.040

To evaluate patients with hyperprolactinemia for the presence of dopamine receptor D2 polymorphisms. Case-control study. Academic research environment. Women and men with pathologic hyperprolactinemia and healthy controls. DNA extraction of peripheral blood, polymerase chain reaction, single-strand conformation polymorphism, DNA sequencing, and restriction digest. 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). 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. 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.