Genetic Basis of Drug Metabolism

Margaret K. Ma, Michael H. Woo, Howard L. Mcleod


Am J Health Syst Pharm. 2002;59(21) 

In This Article

Common Terminology

DNA consists of four bases: adenine, guanine, thymine, and cytosine. Any combination of three nucleic acids can form a codon, which is transcribed into mRNA and translated into a particular amino acid (e.g., ACG encodes for threonine). The stop codon, TAG, terminates protein synthesis. An incorrectly placed stop codon in a gene, caused by mutation, prematurely truncates an amino acid chain and may form a nonfunctional protein. Many of the variations in the human genome are single base changes, termed SNPs. A mutation of one nucleotide of a codon may result in either a change in the coded amino acid (nonsynonymous SNP) or no change (silent polymorphism or synonymous SNP). Since each person has a pair of each chromosome, he or she has two alleles for each gene, one on each chromosome. Different alleles produce variations in inherited characteristics, such as eye color and blood type. In an individual, one form of the allele (the dominant one) may be expressed more than another form (the recessive one). Two identical alleles result in a homozygous dominant or homozygous recessive trait of that gene. A combination of two different alleles leads to a heterozygous trait. One or more genes that code for a particular protein, such as an enzyme or a receptor, may be expressed in different amounts in different tissues. In this review, all individual alleles (or genes) are referenced by their gene name (e.g., CYP2D6), followed by an asterisk and an Arabic number (e.g., CYP2D6*1 designates the wild-type allele and CYP2D6*3 is a mutant allele).[6]