title: Development of a high throughput single nucleotide polymorphism screening method for the cytochrome P450 1A2 polymorphisms CYP1A2*1C and CYP1A2*1F: are they useful as predictive markers in mental disorders?
abstract: BACKGROUND
  The cytochrome P450 1A2 (CYP1A2) gene encodes one of the most important enzymes of the Phase I drug metabolism, which is involved in the metabolism of many lipophilic xenobiotics, such as haloperidol, theophylline, phenacetine, and others. The recently discovered single nucleotide polymorphisms CYP1A2*1C (-3860G-->A) in the 5' flanking region of the gene and CYP1A2*1F (-163C-->A) in intron 1 seem to interfere with the expression rate or catalytic function of the enzyme. Polymorphism carriers may either have a risk of reduced drug degradation and side effects, or may present with an increased induction of enzymatic activity resulting in clinical non-response to the prescribed therapy. We investigated two populations, a mental disease group and a healthy control group, to identify whether these two genetic variants are correlated with the general development of a mental disorder and if they could potentially be used as predictive markers for manifestation of the same.
  
  
  METHODS
  Using specifically designed primers, we established a high-throughput multiplex screening realtime PCR method for the two polymorphisms on the CYP1A2 gene with the Roche LightCycler instrument.
  
  
  RESULTS
  We analysed the two cohorts to identify whether one of the two described genetic variants may be associated with the manifestation of a mental disorder in general. For the CYP1A2*1C variant, we identified an allele frequency of 1.7% for both cohorts. For the CYP1A*1F polymorphism, we found an allele frequency of 74.5% for the mental disease group and 68.6% for the healthy control group.
  
  
  CONCLUSIONS
  This new diagnostic method of multiplex detection may be helpful to routinely identify carriers of CYP1A2 variants and to improve the therapeutic effectiveness by selection of the most appropriate therapeutic regimen. As a result of this pilot study, there appeared to be no significant correlation between the existence of one of the investigated genetic variants and the development of a mental disorder.
authors.affiliation: PharmGenomics GmbH, Mainz, Germany. marco.klemm@pharmgenomics.com
authors.forename: Marco
authors.initials: M
authors.lastname: Klemm
authors.forename: Moritz
authors.initials: M
authors.lastname: Eidens
authors.forename: Marion
authors.initials: M
authors.lastname: Lorenz
authors.forename: Stefan
authors.initials: S
authors.lastname: Prause
authors.forename: Alexander
authors.initials: A
authors.lastname: Weise
authors.forename: Norbert
authors.initials: N
authors.lastname: Dahmen
authors.forename: Thomas
authors.initials: T
authors.lastname: Forst
authors.forename: Andreas
authors.initials: A
authors.lastname: Pfützner
mesh_terms: D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D005819:Genetic Markers; D006801:Humans; D007438:Introns / Q000235:genetics; D001523:Mental Disorders / Q000235:genetics*; D009691:Nucleic Acid Denaturation; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide
chemical_list: D005819:Genetic Markers; D004247:DNA; D019388:Cytochrome P-450 CYP1A2