title: Lack of impact of CYP1A2 genetic polymorphism (C/A polymorphism at position 734 in intron 1 and G/A polymorphism at position -2964 in the 5'-flanking region of CYP1A2) on the plasma concentration of haloperidol in smoking male Japanese with schizophrenia.
abstract: The impact of genetic polymorphism of CYP1A2 that are related to the induction of the isozyme on the plasma levels of haloperidol (HAL) in 40 male smokers with schizophrenia was investigated. A point mutation from C to A in intron 1 at position 734 and a point mutation from G to A at position -2964 in the 5'-flanking region of CYP1A2 were identified by polymerase chain-reaction-restricted fragment length polymorphism method. Regarding C/A polymorphism in intron 1 at position 734, no significant difference was found in the plasma concentrations of HAL corrected for dose and weight among the subjects with A/A (n = 21), A/C (n = 14) and C/C (n = 5) genotypes (one-way analysis of variance: 63.1 +/- 18.5, 47.8 +/- 12.5 and 50.8 +/- 15.1 ng/ml/mg/kg, respectively, F(2,37) = 2.556, P = .09). Regarding G/A polymorphism at position -2964 in the 5'-flanking region, no significant difference was found in the plasma concentrations of HAL corrected for dose and weight between subjects with G/G (n = 24) and G/A (n = 15) (two-tailed t test: G/G and G/A = 51.2 +/- 16.6 and 59.0 +/- 17.6 ng/ml/mg/kg, respectively, df = 28, P = .22). The present study suggests that the genotyping of CYP1A2 cannot predict the steady state plasma levels of HAL in male smoking schizophrenics.
authors.affiliation: Department of Psychiatry, Shiga University of Medical Science, Otsu, Japan. shimoda@belle.shiga-med.ac.jp
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Shimoda
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Someya
authors.forename: Sachiyo
authors.initials: S
authors.lastname: Morita
authors.forename: Genta
authors.initials: G
authors.lastname: Hirokane
authors.forename: Aya
authors.initials: A
authors.lastname: Yokono
authors.forename: Saburo
authors.initials: S
authors.lastname: Takahashi
authors.forename: Masako
authors.initials: M
authors.lastname: Okawa
mesh_terms: D024506:5' Flanking Region / Q000235:genetics; D000225:Adenine; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000097:blood; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis / Q000235:genetics*; D003596:Cytosine; D004790:Enzyme Induction / Q000235:genetics; D006147:Guanine; D006220:Haloperidol / Q000097:blood*; D006801:Humans; D007438:Introns / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D012559:Schizophrenia / Q000097:blood* / Q000201:enzymology / Q000235:genetics*; D012907:Smoking / Q000097:blood*
chemical_list: D014150:Antipsychotic Agents; D006147:Guanine; D003596:Cytosine; D019388:Cytochrome P-450 CYP1A2; D006220:Haloperidol; D000225:Adenine