Pharmacogenomics and clinical application in neuropsychological disorders

Pharmacogenetics is generally regarded as the study or clinical testing of genetic variation that gives rise to differing response to drugs, while pharmacogenomics is the broader application of genomic technologies to new drug discovery and further characterization of older drugs. Pharmacogenomics study focuses on the relationship between genes and drugs. This is new scientific discipline made possible by the genome project. Pharmacogenomics holds the promise that drugs might one day be tailor-made for individuals and adapted to each personʹs own genetic makeup. Environment, diet, age, lifestyle, and state of health all can influence a personʹs response to medicines, but understanding an individualʹs genetic makeup is thought to be the key to creating personalized drugs with greater efficacy and safety. The first observations of genetic variation in drug response date from the 1950s, involving the muscle relaxant suxamethonium chloride, and drugs metabolized by Nacetyltransferase. One in 3500 Caucasians has less efficient variant of the enzyme (butyrylcholinesterase) that metabolizes suxamethonium chloride. As a consequence, the drug’s effect is prolonged, with slower recovery from surgical paralysis. Variation in the N-acetyltransferase gene divides people into “slow acetylators” and “fast acetylators”, with very different half-lives and blood concentrations of such important drugs as isoniazid (antituberculosis) and procainamide (antiarrhythmic). As part of the inborn system for clearing the body of xenobiotics, the cytochrome P450 oxidases (CYPs) are heavily involved in drug metabolism, and genetic variations in CYPs affect large populations. One member of the CYP super family, CYP2D6, now has over 75 known allelic variations, some of which lead to no activity, and some to enhanced activity. An estimated 29% of people in parts of East Africa may have multiple copies of the gene, and will therefore not be adequately treated with standard doses of drugs such as the painkiller codeine (which is activated by the enzyme). The wder use of pharmacogenetic testing is viewed by many as an outstanding opportunity to improve prescribing safety and efficacy. Driving this trend are the 106,000 deaths and 2.2 Million serious events caused by adverse drug reactions in the US each year. As such ADRs are responsible for 5-7% of hospital admissions in the US and Europe, lead to the withdrawal of 4% of new medicines and cost society an amount equal to the costs of drug treatment. One such example is look at drug effect and side effect. Why some individuals experience side effects to some drugs while others respond well with no adverse reaction to the same drug. As first study of pharmacogenetics study we focus on neuropsychological disorders such as Schizopherenia patients. The gene target for this study was neurotransmitter genes. The antagoanist and goanist of this gene are available and approved by FDA. We investigated dopamine receptors genes expression in PBMC of schizophrenia patients before and after treatment. Also dopamine receptor genes expression profiles were compared in two treatment groups included haloperidol and olanzapine. The PBMC was separated from whole blood by Ficoll-hypaque; the total cellular RNA was extracted and the cDNA was synthesized. This process followed by real-time PCR using primer pairs specific for five dopamine receptors mRNAs and β-actin as internal control. The results show the presence of all types of dopamine receptors on lymphocytes. Dopamine genes expression profile in D2 and D4 were shown significant changes that were correlated with kind of treatment and GCI score improvement. In conclusion, the present study has shown that pharmacogenetics study may help physicians to make patients treatment individually. Moreover, investigated dopamine receptors genes expression in PBMC of treated schizophrenic patients correlated with clinical symptom improvement.