Human Genomic Population Structure and Phenotype-genotype Variation in ADME Genes in Four Populations
Exploratory Study of the Variability, in Five Human Populations, of ADME (Administration, Distribution, Metabolism, Excretion) Genotypes and Phenotypes After the Intake of the "Geneva Micrococktail"
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.
研究概览
研究类型
注册 (实际的)
阶段
- 不适用
联系人和位置
学习地点
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Addis Ababa、埃塞俄比亚、P.O.Box 9086
- Addis Ababa University/College of Health Sciences
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Alexandroupolis、希腊、68100
- Democritus University of Thrace/School of Health Sciences/University Campus, Dragana
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Praha 2、捷克语、128 43
- Charles University in Prague/Faculty of Science/Department of Anthropology and Human Genetics
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Muscat、阿曼、P. O. Box 50
- Sultan Qaboos University/College of Medicine and Health Sciences/Department of Pharmacology
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
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.);
学习计划
研究是如何设计的?
设计细节
- 主要用途:基础科学
- 分配:非随机化
- 介入模型:并行分配
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:Healthy volunteers in Ethiopia
Phenotype and genotype of enzymes involved in drug metabolism in Ethiopia population
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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
DNA sampling from a saliva sample
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实验性的:Healthy volunteers in Oman
Phenotype and genotype of enzymes involved in drug metabolism in Oman population
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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
DNA sampling from a saliva sample
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实验性的:Healthy volunteers in the Czech Republic
Phenotype and genotype of enzymes involved in drug metabolism in Czech Republic population
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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
DNA sampling from a saliva sample
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实验性的:Healthy volunteers in Greece
Phenotype and genotype of enzymes involved in drug metabolism in Greek population
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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
DNA sampling from a saliva sample
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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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
大体时间:through study completion, an average of 2 years
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Estimation of genotype/allele/haplotype frequencies of variants in genes involved in drug responses
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through study completion, an average of 2 years
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Activities of 6 cytochrome P450 enzymes and P-gp in 4 human populations : 100 Ethiopian, 100 Omani, 100 Czech and 100 Greek
大体时间:through study completion, an average of 2 years
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Estimation of frequency distributions of classes of drug metabolizers (metabolizers' profiles: slow/normal/rapid)
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through study completion, an average of 2 years
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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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
大体时间:through study completion, an average of 3 year
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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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through study completion, an average of 3 year
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合作者和调查者
调查人员
- 学习椅:Estella S. Poloni, Dr、University of Geneva/Department of Genetics and Evolution
出版物和有用的链接
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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