Dopamine D4 and D5 receptor gene variant effects on clozapine response in schizophrenia: replication and exploration.
OBJECTIVE
This study aimed to: 1) replicate previously reported associations between dopamine D4 receptor gene (DRD4) polymorphisms and antipsychotic (AP) response in a clozapine (CLZ) response sample; and 2) explore possible associations of polymorphisms across dopamine D5 receptor gene (DRD5) as well as other DRD4 regions.


METHODS
DRD4 exon III 48-bp, intron I (G)(n), and 120-bp repeat polymorphisms, and three DRD4 single nucleotide polymorphisms (SNPs); and DRD5 (CA/CT/GT)(n) microsatellite and four DRD5 SNPs were assessed using standard genotyping and statistical procedures.


RESULTS
We report evidence, which does not survive correction for multiple testing, supporting previous DRD4 findings. Findings of interest include the 120-bp 1-copy allele, intron I (G)(n) 142-bp/140-bp genotype, and exon III 4R allele with CLZ response. All DRD5 tests were negative.


CONCLUSIONS
Overall, these results suggest a possible minor contribution of DRD4 variants, but not DRD5 variants, towards the AP/CLZ response phenotype.
Neurogenetics Section, Centre for Addiction and Mental Health, Toronto, ON, Canada. rudirudi@gmail.com
Rudi
R
Hwang
Arun K
AK
Tiwari
Clement C
CC
Zai
Daniel
D
Felsky
Eli
E
Remington
Tessa
T
Wallace
Ryan P
RP
Tong
Renan P
RP
Souza
Gabriel
G
Oh
Steven G
SG
Potkin
Jeffrey A
JA
Lieberman
Herbert Y
HY
Meltzer
James L
JL
Kennedy
D014150:Antipsychotic Agents / Q000627:therapeutic use; D044383:Black People / Q000235:genetics; D003024:Clozapine / Q000627:therapeutic use*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011446:Prospective Studies; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D050641:Receptors, Dopamine D5 / Q000235:genetics*; D012559:Schizophrenia / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics*; D016896:Treatment Outcome; D044465:White People / Q000235:genetics
D014150:Antipsychotic Agents; D050638:Receptors, Dopamine D4; D050641:Receptors, Dopamine D5; D003024:Clozapine