Pharmacogenetics and Pharmacogenomics in Personalized Medicine: Role of Gene Polymorphism in Drug Response

Magnitude of the information regarding pharmacogenetics and pharmacogenomics with increasing knowledge in the field of molecular biology has profoundly augmented day-by-day for giving the best-tailored medication to the patients in a most effective way with less involvement of cost and time. It is well understood and recognized that with the same kind of medication, different patients predisposed to a same kind of disease would respond in a different manner. Human genome project has been completed in 2003, there are only 20,000-25,000 genes, which are much less in number than it was expected or hypothesized. More than 1.4 million single-nucleotide polymorphisms were identified in the initial sequencing of the human genome (Sachidanandam et al., 2001) for genotyping and phenotyping studies. Of them, over 60,000 have been identified in the coding region of genes. Some of these single-nucleotide polymorphisms (SNPs or also called “snips”) have been reported to be associated with substantial changes in the metabolism or effects of medications and some are being used to predict clinical response (Evans et al., 1960; Evans and Relling, 1999; Evans and Johnson, 2001; McLeod and Evans, 2001). Depending on the nature of the protein required to perform a specific biological functions, the exons of the assigned genes are tagged together by splicing and then expressed. Each codon within the gene determines the nature of the amino acid and any change in a single base in the codon that may change the open reading frame of the codon followed by a change in amino acid, which could ultimately alter whole structure of the three dimensional structure of protein. As a result, response of the expressed protein towards its substrate or ligand will also be altered that ultimately cause reduction or unnecessary augmentation of function. Thus, genes determine the structural and functional properties of all body proteins, and the efficacy of medicines, as medicines work on body proteins. So, the response to a particular medicine is different in different people due to variations in genetic makeup. It is estimated that genetics can account for 20 to 95% of variability in drug disposition and effects (Kalow et al., 1998; Evans and McLeod, 2003) although many nongenetic factors such as age, organ function, concomitant therapy, drug interactions, and the nature of the disease influence the effects of medications (Evans and Relling, 1999). Interindividual differences in drug response are due to sequence variants in genes encoding drug-metabolizing enzymes, drug transporters, or drug targets (Evans and Johnson, 2001; McLeod and Evans, 2001). That’s why personalized medicine is a concerned topic of recent days. Although many people are in favor of personalized medicine, few of them understand exactly what it is, how to invent it and how to use it. Personalized medical treatment expects the best possible outcomes by providing the right treatment to the right person in the right amount at the right time. Thus, personalized medicine is the use of genetic or other molecular biomarker information to improve the safety, effectiveness and health outcomes of patients via more efficiently targeted risk stratification, prevention and tailored treatment management approaches.