RLO: Pharmacogenomics

• Introduction
• Variation In Drug Responses
• Pharmacogenetic Variation
• Clinical Implications
• Pharmacogenetic Testing In Cancer
• The Future

Pharmacogenetic Variation

Most of the genetic variants that affect drug action are single nucleotide polymorphisms (SNPs), or sets of closely linked SNPs called haplotypes. SNPs are commonly occurring single-nucleotide substitutions of one base for another, present in at least 1% of the general population. However, haplotypes are generally better predictors of drug responsiveness than isolated SNPs. For example, if responsiveness to a particular drug Y is affected by a set of SNPs in gene X, and there are five commonly occurring haplotypes (combinations of these SNPs) in a population, then two might be associated with good responses, one with moderately good responses, and two with poor responses. Thus using real-life illustrations, there are two common variants, C or T, at a specific position in the multidrug transporter gene ABCB1. Most individuals will have the genotype CC, CT or TT with respect to this SNP, and the CC genotype has been associated with resistance to anti-epileptic drugs.