Assay for the simultaneous detection of the *1C and *1F alleles of the CYP1A2 gene by real-time polymerase chain reaction and melting curve analysis.
Pharmacogenetic variation is an important factor in the therapeutic outcome of many drug treatments. The cytochrome P450 isoform CYP1A2 is involved in the metabolism of a number of antipsychotic drugs. Variable expression of this enzyme may result in idiosyncratic drug responses, including adverse reactions. A number of DNA sequence polymorphisms have been identified in the CYP1A2 gene. Of these, two alleles, CYP1A2*1C and CYP1A2*1F, have been linked to changes in gene expression among smokers. In addition, these polymorphisms have been linked to susceptibility to tardive dyskinesia in some patient populations receiving antipsychotic drug therapy. Here, we present a rapid and robust method for simultaneously genotyping the CYP1A2*1C and *1F alleles using fluorescent hybridization probes and a widely available real-time polymerase chain reaction platform. Such an assay would offer the opportunity to routinely establish the CYP1A2 genotype of a patient prior to commencing drug therapy.
Casley
William L
WL
Centre for Biologics Research, Biologics and Genetic Therapies Directorate, Health Canada, Ottawa, Ontario, Canada. bill_casley@hc-sc.gc.ca
LeBlanc-Westwood
Carole A
CA
D000483:Alleles; D014150:Antipsychotic Agents / Q000493:pharmacokinetics; D003199:Computer Systems; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004247:DNA / Q000032:analysis / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics; D005838:Genotype; D006358:Hot Temperature; D006801:Humans; D009691:Nucleic Acid Denaturation; D016133:Polymerase Chain Reaction / Q000379:methods*; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D012559:Schizophrenia / Q000188:drug therapy / Q000235:genetics; D012680:Sensitivity and Specificity; D012907:Smoking / Q000235:genetics
D014150:Antipsychotic Agents; D004247:DNA; D019363:Cytochrome P-450 CYP1A1