The study of pharmacogenomics profiling of the Kazakhstan population using next-generation sequencing
Project Status: 3 Approved without Funding
Duration in months: 36 months
Objective
The project will study pharmacogenomic profiles of the Kazakhstan population using next-generation DNA sequencing.
The project will accomplish this by: Collection of DNA samples from healthy volunteers. Information analysis of candidate genes involved in drug metabolism. Design of a screening panel using Ion AmpliseqTM Designer. Screening for nucleotide polymorphisms in candidate genes involved in drug metabolism. Bioinformatics analysis and validation of the data.
Implementation of the project will help to solve a number of fundamental and applied problems in the field of pharmacogenomics and medicine. The obtained results will expand knowledge in area of the pharmacogenomics of the Kazakh and Russian populations. A wide range of SNPs and polymorphisms of genes involved in the metabolism of drugs will be studied to highlight specific markers for evaluation of the effectiveness of drugs. Implementation of the project objectives, including bioinformatics analysis and data validation, will be carried out together with the collaborator, as well as discussion of the results and preparation of the joint articles.
According to the World Health Statistics, there is a risk of side effects from the therapy drugs that in some cases may lead to death. There are no statistics on drugs adverse side effects in Kazakhstan; however, incidence of side effects in clinical practice is present. Application of methods of pharmacogenomics allows predicting the response of the patient to the drug to avoid side effects. It makes possible prescription of the most effective drug therapy.
Currently, pharmacogenomics is one of the most relevant areas of research, as it allows solving a number of scientific and clinical challenges in medicine. It is primarily associated with the selection of the most effective and safe therapy for patients. Pharmacogenomics plays an important role in determining the variability of the clinical response of patients to drugs, the risk of side effects, correction of dose, the mechanism of action of the drug. It also helps to identify polymorphic target genes involved in drug metabolism. Pharmacogenomics is an integral part of personalized medicine, as it provides information about each patient.
According to the US Food and Drug Administration (FDA), European Medicines Agency (EMA), and the Pharmaceuticals and Medical Devices Agency (PMDA), there is a wide range of drugs that should be administered to patients only after genetic analysis. Drug labels may contain information about genetic biomarkers and can describe characteristics, dosage and use, warnings and precautions, side effects, data from clinical pharmacology and clinical research.
There are many pharmacological diagnostic services on the market detecting genetic markers responsible for the efficient metabolism, transport, inactivation, and excretion of drugs. There are online tools (e.g., http://warfarindosing.org) to help doctors and other clinicians calculate dosage of various drugs. Genetic diagnostics is based on population data sets, such as the European, Asian and African-American. Each ethnic group carries specific genetic features, depending on ancestry, geography, environmental factors, etc.
A study of population genetics of Kazakhs is underway, referring to the known genetic markers from other Asian populations (Chinese, Japanese, etc.). This approach is not suitable for detection of new genetic markers associated with the absence of the therapeutic effect or side effects in the population.
Implementation of the objectives will include informational analysis of candidate genes involved in drug metabolism, creation of the pharmacogenomic screening panel, screening of polymorphisms in the candidate genes and bioinformatics analysis that enables identification of de novo polymorphisms, typical for the Kazakh and Russian populations. The results obtained by this project will form the scientific basis for effective drug therapy.
All participants of the project are competent in this area. They have been implementing projects in the field of pharmacogenomics, carried out genotyping of the Kazakh population, developed testing kits for the effective treatment of warfarin and clopidogrel in patients with cardiovascular disease.
Expected Results and Their Application.
- To obtain data on genetic polymorphisms in the Kazakh and Russian populations;
- To establish the genetic variability of candidate genes involved in drug metabolism; create a new database of genetic markers involved in the metabolism of drugs in Kazakhstan;
- To predict the effectiveness of drugs in patients with various diseases;
- To improve medical services by using scientifically based prediction algorithms and confirm the effectiveness of drugs based on genotyping, thus avoiding the occurrence of adverse clinical incidents and decreasing the cost of medical services;
The above set of results of the project will help to apply these genetic markers of drug metabolism to predict the risk of side effects and to select optimal and effective drug therapy.
