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| Name | Class |
|---|---|
| Swiss National Science Foundation | OTHER |
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Physicians know that their patients can react differently to the same medical treatment: for some of them, the drug will prove inefficient, whereas for others it might provoke side-effects, sometimes rather serious. Such differences in response to drug intake are due to several factors, of which molecular variations in specific genes, named " ADME " (Absorption, Distribution, Metabolism, Excretion). This project aims at investigating the evolutionary mechanisms responsible for the diversity of ADME genes in human populations. Because of their role at the interface between the organism and its chemical environment, ADME genes are likely targets of recent selective pressures linked to changes in the environments in which humans evolved, such as changes in dietary habits for instance.
The aim of this project is to study the diversity of ADME genes and of their expression in five populations located along a latitudinal axis that extends from East Africa to Central Europe, passing through the Arabian Peninsula and the Mediterranean area, so as to take into account environmental factors that might have influenced the evolution of this diversity. This project is thus intended to evidence the evolutionary mechanisms that shaped genomic regions that are functionally important from the clinical and epidemiological point of view. Moreover, it will allow us to extend the knowledge of human molecular diversity and its evolution to a key-region of the peopling history of our species.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy volunteers in Ethiopia | Experimental | Phenotype and genotype of enzymes involved in drug metabolism in Ethiopia population |
|
| Healthy volunteers in Oman | Experimental | Phenotype and genotype of enzymes involved in drug metabolism in Oman population |
|
| Healthy volunteers in the Czech Republic | Experimental | Phenotype and genotype of enzymes involved in drug metabolism in Czech Republic population |
|
| Healthy volunteers in Greece | Experimental | Phenotype and genotype of enzymes involved in drug metabolism in Greek population |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Phenotyping | Drug | finger-tip blood drop : enzymatic activities assessed by specific single point concentration ratios after oral intake of the Geneva micrococktail made of : CYP1A2: paraxanthine/caffeine CYP2B6: 4-hydroxybupropion/bupropion CYP2C9: 4-hydroxyflurbiprofen/flurbiprofen CYP2C19: 5-hydroxyomeprazole/omeprazole CYP2D6: dextrorphan/dextromethorphan CYP3A4: 1-hydroxymidazolam/midazolam |
| Measure | Description | Time Frame |
|---|---|---|
| Frequencies of genotypes and haplotypes of genes involved in drug responses (240,000 Single Nucleotide Polymorphisms) in 4 human populations : 100 Ethiopian, 100 Omani, 100 Czech and 100 Greek | Estimation of genotype/allele/haplotype frequencies of variants in genes involved in drug responses | through study completion, an average of 2 years |
| Activities of 6 cytochrome P450 enzymes and P-gp in 4 human populations : 100 Ethiopian, 100 Omani, 100 Czech and 100 Greek | Estimation of frequency distributions of classes of drug metabolizers (metabolizers' profiles: slow/normal/rapid) | through study completion, an average of 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Comparison of frequency distributions of variants in genes involved in drug responses and of associated metabolizers' profiles in 4 human populations : 100 Ethiopian, 100 Omani, 100 Czech and 100 Greek | Estimation of indices of population genetic/phenotypic diversity and differentiation (expected heterozygosity, Fst). Inferences on the evolutionary mechanisms explaining the estimated diversity among and between populations. |
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Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Estella S. Poloni, Dr | University of Geneva/Department of Genetics and Evolution | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Charles University in Prague/Faculty of Science/Department of Anthropology and Human Genetics | Prague | 128 43 | Czechia | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32851583 | Derived | Rollason V, Mouterde M, Daali Y, Cizkova M, Priehodova E, Kulichova I, Posova H, Petanova J, Mulugeta A, Makonnen E, Al-Habsi A, Davidson R, Al-Balushi KK, Al-Thihli K, Cerna M, Al-Yahyaee S, Cerny V, Yimer G, Poloni ES, Desmeules J. Safety of the Geneva Cocktail, a Cytochrome P450 and P-Glycoprotein Phenotyping Cocktail, in Healthy Volunteers from Three Different Geographic Origins. Drug Saf. 2020 Nov;43(11):1181-1189. doi: 10.1007/s40264-020-00983-8. |
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| ID | Term |
|---|---|
| D016130 | Immunophenotyping |
| D005838 | Genotype |
| ID | Term |
|---|---|
| D007159 | Immunologic Tests |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
| D003933 | Diagnosis |
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| Genotyping | Genetic | DNA sampling from a saliva sample |
|
| through study completion, an average of 3 year |
| Addis Ababa University/College of Health Sciences |
| Addis Ababa |
| P.O.Box 9086 |
| Ethiopia |
| Democritus University of Thrace/School of Health Sciences/University Campus, Dragana | Alexandroupoli | 68100 | Greece |
| Sultan Qaboos University/College of Medicine and Health Sciences/Department of Pharmacology | Muscat | P. O. Box 50 | Oman |
| D008919 | Investigative Techniques |
| D007158 | Immunologic Techniques |
| D055614 | Genetic Phenomena |