title: Association of DRD2 and ANKK1 polymorphisms with prolactin increase in olanzapine-treated women.
abstract: 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.
  
  
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authors.affiliation: Lilly USA LLC., Indianapolis, IN, USA. houstonjp@lilly.com
authors.forename: John
authors.initials: J
authors.lastname: Houston
authors.forename: Sweta
authors.initials: S
authors.lastname: Dharia
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Bishop
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Ellingrod
authors.forename: Bonnie
authors.initials: B
authors.lastname: Fijal
authors.forename: Jennie G
authors.initials: JG
authors.lastname: Jacobson
authors.forename: Vicki P
authors.initials: VP
authors.lastname: Hoffmann
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use*; D004338:Drug Combinations; D005260:Female; D005473:Fluoxetine / Q000627:therapeutic use; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D000077152:Olanzapine; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011388:Prolactin / Q000097:blood*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011618:Psychotic Disorders / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012727:Sex Characteristics
chemical_list: D014150:Antipsychotic Agents; D004338:Drug Combinations; D017448:Receptors, Dopamine D2; C492572:olanzapine-fluoxetine combination; D005473:Fluoxetine; D001569:Benzodiazepines; D011388:Prolactin; C489948:ANKK1 protein, human; D017346:Protein Serine-Threonine Kinases; D000077152:Olanzapine