Dopamine D2 receptors, encoded by DRD2, play a role in regulating serum prolactin concentration. Single nucleotide polymorphisms (SNPs), rs2734842(C), rs6275(T), and rs6279(C) located within DRD2, have been shown to be associated with prolactin increase in olanzapine/fluoxetine combination (OFC)-treated women. The present analyses seek to replicate these results and test other SNPs in DRD2 and neighboring gene ANKK1 for associations with prolactin increase in women, using data from 3 pooled studies of olanzapine, and 2 previously examined studies OFC. An ANCOVA was used to test whether change from baseline in the natural log of prolactin concentration (ln[prolactin]) was associated with SNPs in the pooled olanzapine studies. A meta-analysis was also performed using the inverse chi-square method, pooling p-values from the 2 previously examined studies and the 3 olanzapine studies. Negative strand alleles rs2734842(C), rs6275(T), and rs6279(C) were significantly associated with increased prolactin in olanzapine-treated women, replicating previous results. These SNPs also showed moderate association with increased prolactin in olanzapine-treated and OFC-treated women in the meta-analysis, as did rs4938016, rs2734848, rs2734841, rs1124493, and rs1076562. Five of these SNPs fall in or are adjacent to an LD block spanning DRD2 intron 7, exon 7, 5' untranslated region and ANKK1.Clinical trial Registration: www.clinicaltrial.govStudy A: NCT00091650Study B: NCT00088036Study C: NCT00094549Study D: NCT00035321Study E: NCT00485771.
Bibliographical noteFunding Information:
Drs. Houston, Fijal, Jacobson and Hoffmann are employees of Eli Lilly and Company or one of its subsidiaries and are and minor stockholders in Eli Lilly and Company. Ms. Dharia is an employee of i3 Statprobe, which is under contract with Eli Lilly and Company. Dr. Bishop has received grant funding from Ortho McNeil Janssen and honoraria from Eli Lilly. Dr. Ellingrod is a former advisory board member for Eli Lilly and Company.
- Antipsychotic agents
- Dopamine receptors