title: Multiplex genotyping of CYP3A4, CYP3A5, CYP2C9 and CYP2C19 SNPs using MALDI-TOF mass spectrometry.
abstract: BACKGROUND
  Pharmacogenetics is the study of genetic variations that cause alterations in drug level, drug response and adverse drug reactions. SNPs found in CYP450 genes have the greatest genetic influences on interindividual variability in drug bioavailability. The polymorphic nature of these genes may modulate several enzyme levels that affect individual responses to pharmacological treatment. Among them, CYP3A4, CYP3A5, CYP2C9 and CYP2C19 isoforms of CYP450 enzymes are involved in the metabolism of many commonly prescribed drugs.
  
  
  OBJECTIVE
  In this study, we would like to develop a CYP450 genotyping platform that could lead a complete definition of a patient's metabolic genotype in order to improve the clinical outcome of some drug treatments.
  
  
  METHODS
  We used matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) (Sequenom) to develop a SNP genotyping method.
  
  
  RESULTS
  This MALDI-TOF-based multiplexing system allows the simultaneous and efficient genotyping of a set of CYP450 gene polymorphisms.
  
  
  CONCLUSIONS
  The multiple CYP450 gene testing achieved with this application can be used to develop diagnostic tests to predict drug responses and clinical outcomes.
authors.affiliation: Istituto Tecnologie Biomediche del Consiglio Nazionale delle Ricerche CNR-ITB, Parco Scientifico e Tecnologico della Sardegna, Ed. 5, Loc. Piscinamanna, 09010 Pula (CA) Italy. matteo.falzoi@pharmaness.it
authors.forename: Matteo
authors.initials: M
authors.lastname: Falzoi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mossa
authors.forename: Elena
authors.initials: E
authors.lastname: Congeddu
authors.forename: Luisella
authors.initials: L
authors.lastname: Saba
authors.forename: Luca
authors.initials: L
authors.lastname: Pani
mesh_terms: D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001483:Base Sequence; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D004247:DNA / Q000032:analysis; D005787:Gene Frequency; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D044465:White People / Q000235:genetics*
chemical_list: D004247:DNA; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; C510164:CYP3A5 protein, human; D065731:Cytochrome P-450 CYP2C19; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human