Human Genomic Population Structure and Phenotype-genotype Variation in ADME Genes in Four Populations

Estella S. Poloni

Status: Completed

Conditions: Healthy

Treatments: Drug: Phenotyping; Genetic: Genotyping

Study type: Interventional

Funder types: Other

Identifiers

NCT02789527

15-169

Details and patient eligibility

About

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.

Enrollment: 367 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Women and men in good health
• Aged between 18 and 50 years
• Students or staff in the Academic Institutions where sampling will take place
• With the 2 parents and four grand-parents born to the population;
• Able to provide informed consent

Exclusion criteria

• Pregnant or breastfeeding women; or women that consider that being pregnant is a possibility;
• Allergic to one of the compounds included in micrococktail (Caffeine, Bupropion, Flurbiprofen, Omeprazole, Dextromethorphan, Midazolam, and Fexofenadine);
• Pedigree related to another volunteer participant (siblings, cousins, uncles/aunts, nephews, etc.);

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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367 participants in 4 patient groups

Healthy volunteers in Ethiopia

Experimental group

Description:

Phenotype and genotype of enzymes involved in drug metabolism in Ethiopia population

Treatment:

Genetic: Genotyping

Drug: Phenotyping

Healthy volunteers in Oman

Experimental group

Description:

Phenotype and genotype of enzymes involved in drug metabolism in Oman population

Treatment:

Genetic: Genotyping

Drug: Phenotyping

Healthy volunteers in the Czech Republic

Experimental group

Description:

Phenotype and genotype of enzymes involved in drug metabolism in Czech Republic population

Treatment:

Genetic: Genotyping

Drug: Phenotyping

Healthy volunteers in Greece

Experimental group

Description:

Phenotype and genotype of enzymes involved in drug metabolism in Greek population

Treatment:

Genetic: Genotyping

Drug: Phenotyping