Determination of −3858G→A and −164C→A genetic polymorphisms of CYP1A2 in blood and saliva by rapid allelic discrimination: large difference in the prevalence of the −3858G→A mutation between Caucasians and Asians
The effect of a genetic polymorphism of inducibility of cytochrome P450 (CYP) 1A2 on the steady state plasma concentrations (Css) of haloperidol and reduced haloperidol was studied to clarify if these Css are dependent on the CYP1A2 activity. The subjects were 101 Japanese schizophrenic inpatients receiving oral haloperidol 12 mg/d. The Css of haloperidol and reduced haloperidol were measured in duplicate by high performance liquid chromatographic method, and were corrected to the mean body weight. A point mutation from guanine (wild-type) to adenine (mutated-type) at position -2964 in the 5'-flanking region of CYP1A2 gene was identified by polymerase chain reaction (PCR)-fragment length polymorphism method. Based on the present results, i.e., significant effects of CYP2D6 genotypes on the Css of haloperidol and reduced haloperidol, analyses were separately performed in two groups, i.e., patients with 0 mutated allele of the CYP2D6 (41 cases) and those with 1 or 2 mutated alleles (60 cases). Subjects in each CYP2D6 genotype group consisted of 4 subgroups according to smoking habit and the presence of the mutated allele of the CYP1A2. Neither the Css of haloperidol nor that of reduced haloperidol significantly differed among the 4 subgroups in either CYP2D6 genotype group. The present study thus suggests that the CYP1A2 activity does not play an important role in controlling the Css of haloperidol or reduced haloperidol.