Epigenetic techniques in pharmacogenetics

Pharmacoepigenetics is an emerging field, which can be studied by several approaches. Addressing DNA methylation status of drug-metabolizing enzymes and transporters (DMET) is challenging and might provide answers in relation to interindividual differences in pharmacokinetics and pharmacodynamics. Studying genetic variation in DMET genes in relation to drug response has been the main focus of pharmacogenetics laboratories; it is, however, expected that epigenetic modifications will play a role in drug responses as well. Some of the variations in drug-responses cannot be explained by genetic variation in DMET genes. For those particular genes it might be interesting to examine the DNA methylation status in relation to pharmacokinetics. In this chapter we discuss the methods available and provide a protocol to quantify DNA methylation status of CpG sites in candidate genes, which can readily be applied to most pharmacogenetics laboratories. In addition, we provide details about optimization and validation of the method in terms of technical specificity and technical sensitivity and precision of the method.

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