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Pharmacogenetics of diabetes and cardiovascular diseases, testing of therapeutic target-receptors

Funding: State Research Programme "Development of advanced prevention strategies, treatment, diagnostic tools and methods, biomedical technologies for improving public health":

Period: 2010-2014

Head of subproject: Dr. biol. Jānis Kloviņš

Aim

Pharmacogentic evaluation of drugs used to treat type 2 diabetes (T2D) and other obesity- related diseases. Develop new diagnostic tests for drug target genes. Design and synthesis of new therapeutics for G protein coupled receptors (GPCRs).

Tasks

1) Carry out clinical observation of patients with T2D and metabolic syndrome in order to evaluate the efficacy and side effects of biguanide and glitazone. Evaluate the potentional role of inflammation- related adipokines and other adipose- derived factors in insulin resistance and development of diabetes complications.

2) Identify genetic profile of the genes that are involved in regulation of drug metabolism of T2D therapeutics in order to create prognostic diagnostic tests for individualized treatment.

3) Study genetic and functional aspects of GPCRs involved in lipolysis/lipogenesis, regulation of adipokine and inflammatory factors secretion. Evaluate their involvement in the development of insulin resistance.

4) Design, synthesis and testing of new and improved ligands for purinergic, niacin and other adipose tissue receptors to treat dyslipidemia, insulin resistance and increased platelet aggregation.

Planned results

Develop pharmacogenetic diagnostic test and recommendations for the best therapy choice based on results from genetic analysis, clinical information and biochemical measurements.

Functional experiments will describe potentional effects of GPCRs in adipocytes that will probably allow to predict the efficacy of used therapeutic combinations.

Association of pro-inflammatory and anti-inflammatory cytokines with clinical diagnostic parameters in patients with liver steatosis and visceral adiposity.

Synthesis of new potentional GPCRs drugs for prevention and treatment of dyslipidemia and diabetes.

Preliminary resultsTo reveal possible effects of individual genetic profile on anti-diabetic therapies the clinical research- Optimal personalized treatment program (OPTIMED) is in progress. The drug therapies are evaluated in T2D patients group by combination of genotyping and detailed phenotyping.



Mājas lapas izstrādi finansēja ERAF 2.1.1.2. aktivitātes projekts Nr. 2010/0196/2DP/2.1.1.2.0/10/APIA/VIAA/004 "Latvijas biomedicīnas pētījumu integrācija Eiropas zinātnes telpā".