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 language | English (US) |
|---|---|
| Pages (from-to) | 711-718 |
| Number of pages | 8 |
| Journal | Fertility and sterility |
| Volume | 84 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 1 2005 |
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Keywords
- Dopamine receptor D
- Hyperprolactinemia
- Pituitary adenomas
ASJC Scopus subject areas
- Reproductive Medicine
- Obstetrics and Gynecology
Cite this
The dopamine receptor D2 genotype is associated with hyperprolactinemia. / Hansen, Keith A.; Zhang, Yueyi; Colver, Robert; Tho, Sandra P.T.; Plouffe, Leo; McDonough, Paul G.
In: Fertility and sterility, Vol. 84, No. 3, 01.09.2005, p. 711-718.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The dopamine receptor D2 genotype is associated with hyperprolactinemia
AU - Hansen, Keith A.
AU - Zhang, Yueyi
AU - Colver, Robert
AU - Tho, Sandra P.T.
AU - Plouffe, Leo
AU - McDonough, Paul G.
PY - 2005/9/1
Y1 - 2005/9/1
N2 - 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.
AB - 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.
KW - Dopamine receptor D
KW - Hyperprolactinemia
KW - Pituitary adenomas
UR - http://www.scopus.com/inward/record.url?scp=24944545645&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=24944545645&partnerID=8YFLogxK
U2 - 10.1016/j.fertnstert.2005.03.040
DO - 10.1016/j.fertnstert.2005.03.040
M3 - Article
C2 - 16169407
AN - SCOPUS:24944545645
VL - 84
SP - 711
EP - 718
JO - Fertility and Sterility
JF - Fertility and Sterility
SN - 0015-0282
IS - 3
ER -