Feng, Xiaodong_ Xie, Hong-Guang - Applying pharmacogenomics in therapeutics-CRC Press (2016)

54 Applying Pharmacogenomics in Therapeutics
Genetic variation
Genetic variants
Nongenetic factors
Environment
Epigenetic variation
DNA methylation
MicroRNAs
Histone modifications
Gene expression
variation
Gene expression
Phenotype variation
Therapeutic response
FIGURE 3.1 Drug response is a complex trait. Individual drug response can be influenced
by various genetic and nongenetic factors, such as genetic variants, epigenetic factors
(e.g., DNA methylation, histone modifications), and environment. Gene expression, a complex
phenotype itself, may be intermediate to drug response phenotypes.
understanding of the mechanisms underlying drug response phenotypes as well as
providing a basis for implementing precision and personalized medicine in clinical
practice. Pharmacogenomics aims to systematically and comprehensively investigate
the genetic architectures of drug response variability by leveraging the great
advances of our scientific knowledge in human genetic variations and the technological
advances, including various microarray- and sequencing-based profiling platforms
13,14 (Figure 3.2).
HUMAN GENETIC VARIATIONS UNDERLIE
PHARMACOGENOMICS
A primary task of pharmacogenomic studies is to identify genetic loci that are
responsible for the clinically observed variability of drug response phenotypes.
Genetic variations within and between human populations, in the forms of single
nucleotide polymorphisms (SNPs) and other structural variants such as copy-number
variants (CNVs), are the basis for pharmacogenomic studies. There are known to be