Relationship between Taq1 A dopamine D2 receptor (DRD2) polymorphism and prolactin response to bromperidol.
The dopamine D2 receptor (DRD2) gene has a Taq1 A restriction fragment length polymorphism yielding two alleles, A1 and A2. We have previously shown that female patients with the A1 allele show greater prolactin response to nemonapride, a selective antagonist for D2-like dopamine receptors, in schizophrenic patients. In the present study, the relationship between this polymorphism and prolactin response to bromperidol was investigated in 32 untreated schizophrenic inpatients (16 males, 16 females). The daily dose of bromperidol was fixed at 6 (n = 10), 12 (n = 13), or 18 mg (n = 9) during a 2-week treatment period. Taq1 A genotypes were determined by PCR method. Plasma prolactin concentration was measured by radioimmunoassay. Plasma concentration of bromperidol was measured by HPLC method. The subjects were divided into four subgroups by gender and the genotypes, i.e., 10 males and 11 females with the A1 allele, 6 males and 5 females with no A1 allele. The females with the A1 allele had the highest Delta prolactin (the change from the pretreatment concentration)/bromperidol concentration ratio among the other groups (P < 0.05). The present study thus suggests that female patients with the A1 allele show greater prolactin response to bromperidol, who may have a high risk for adverse effects associated with neuroleptic-induced hyperprolactinemia.
Mihara
K
K
Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki, Japan.
Suzuki
A
A
Kondo
T
T
Yasui-Furukori
N
N
Ono
S
S
Otani
K
K
Kaneko
S
S
Inoue
Y
Y
D000328:Adult; D000483:Alleles; D015252:Deoxyribonucleases, Type II Site-Specific / Q000235:genetics; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D005838:Genotype; D006220:Haloperidol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D006966:Hyperprolactinemia / Q000139:chemically induced / Q000235:genetics; D007564:Japan; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011388:Prolactin / Q000097:blood / Q000187:drug effects*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics / Q000378:metabolism; D012737:Sex Factors
D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D011388:Prolactin; D015252:Deoxyribonucleases, Type II Site-Specific; C027046:TCGA-specific type II deoxyribonucleases; D006220:Haloperidol; C006820:bromperidol