Multiplex genotyping of CYP3A4, CYP3A5, CYP2C9 and CYP2C19 SNPs using MALDI-TOF mass spectrometry

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. Aims: 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. Materials & 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. Conclusion: The multiple CYP450 gene testing achieved with this application can be used to develop diagnostic tests to predict drug responses and clinical outcomes.