ABSTRACT
Introduction The emergence of pharmacogenomic-guided drug development has led to novel approaches in the effective management of patients and ensured individualized therapy tailored to the needs of one and all, at the right dosage and right time. The entire human genome is now completely mapped. Gene expression profiling and identification of the single nucleotide polymorphism (SNP) will enable effective diagnosis of various diseases, and has a role in preclinical phases of drug development, in developing markers for adverse drug interactions and desired pharmacologic effects. Newer drugs can be withdrawn from the drug development pipeline should they exhibit hepatic metabolism requiring CYP450 enzymes known to manifest SNPs resulting in adverse drug reactions. Vogel for the first time introduced the term, pharmacogenetics, in 1959 (1), which refers to the analysis of monogenetic variants that define an individual’s response to a drug, and aims to deliver the right drug at right dosage to a right patient by using DNA information. The variable drug response in different patients may be the result of genetic differences in drug metabolism, drug distribution, and drug target proteins (2). Pharmacogenetics refers to the entire library of genes that determine drug efficacy and safety. There are approximately three billion base pairs in the human genome that code for at least 30,000 genes. Although the majority of basepairs are identical from individual to individual, only 0.1% of the basepairs contribute to individual differences. Three consecutive basepairs form a codon that specifies the amino acids that constitute the protein. Genes represent a series of codons that specifies a particular protein. At each gene locus, an individual carries two alleles, one
from each parent. If there are two identical alleles, it is referred to as a homozygous genotype, and if the alleles are different, it is heterozygous. Genetic variations usually occur as SNPs and occur on an average of at least once every 1000 basepairs, accounting to approximately three million basepairs distributed throughout the entire genome. Genetic variations that occur at a frequency of at least 1% in the human population are referred to as polymorphisms. Genetic polymorphisms are inherited and monogenic; they involve one locus and have interethnic differences in frequency. Rare mutations occur at a frequency of less than 1% in the human population. Other examples of genetic variations include insertion-deletion polymorphisms, tandem-repeats, defective splicing, aberrant splice site, and premature stop codon polymorphisms. Pharmacogenomics, through the discovery of new genetic targets, is expected to improve the quality of life and control the healthcare costs by treating specific genetic subgroups and by avoiding adverse drug reactions and by decreasing the number of treatment failures. The evolution and the concepts of pharmacoeconomic-based pharmacogenomics and pharmacogenetics should be widely known and practiced. Pharmacogenomics and cheminformatics should become a part of the current study designs of prospective clinical trials. Pharmacogenomic and pharmacogenetic data should be included in the investigational new drug (IND) applications, thereby enabling the food and drug administration (FDA) to evaluate its true impact on pharmacoeconomics resulting in drastic reduction in the healthcare expenditure worldwide. Pharmacogenomics provides a significant paradigm shift in the management of patients and provides a means to increase the quality of medical care.
