Genetic and pharmacogenetic studies in cardiovascular disease: the role of single nucleotide polymorphisms in improving drug therapy
Prospective studies are needed to evaluate whether the use of genetic and phenotypic data to guide drug selection and dosage will result in improved drug safety and efficacy. Although there are many hurdles still to be overcome, the incorporation of pharmacogenetics into clinical medicine is likely to have a great effect on public health in the near future. This raises some important questions: How good are genetic tests at predicting the safety or efficacy of a medicine? How important is genetic variation in determining and/or preventing Adverse Drug Reactions? What are the implications for medicines development and health inequalities? Genetic tests themselves do not predict safety or efficacy of a medicine but rather influence a person’s susceptibility to specific drug metabolite that increase or reduce a possible drug effect. Predictive genomic profiles focused on a carefully selected set of SNPs associated with a particular metabolic pathway or cellular response are needed before consider SNPs clinically useful. To assure clinical value, SNPs included in a pharmacogenetics profile should meet the following criteria: SNPs should have direct influence over specific biochemical pathways which create known effect on drug metabolism; SNPs should have significant population prevalence; SNPs profile should be measurable in terms of functional assessments to evaluate and monitor phenotypic expression of biomarkers; Several studies have shown that both adverse and beneficial responses to cardiovascular drugs can be influenced by SNPs in genes coding for metabolising enzymes, drug transporters and drug targets. Despite the large amount of data about gene-drug interactions, the translation of pharmacogenomics in clinical practise for cardiovascular disorders is slow. There is a need of new technology and large prospective trials allowing for simultaneous analysis of multiple genetic variants in molecular pathways that could affect drug disposition and action.