A population and family study of CYP1A2 using caffeine urinary metabolites
| Autor: | Catherine Bonaïti-Pellié, Y. C. Bechtel, N Poisson, P. R. Bechtel, A Catteau |
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| Rok vydání: | 1995 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Population Biology Genetic determinism Nicotine Cytochrome P-450 Enzyme System Cytochrome P-450 CYP1A2 Internal medicine Caffeine medicine Humans Pharmacology (medical) Enzyme inducer education Aged Pharmacology Genetics education.field_of_study Polymorphism Genetic Smoking CYP1A2 General Medicine Middle Aged Major gene Endocrinology Enzyme Induction biology.protein Population study Female Oxidoreductases Pharmacogenetics medicine.drug Contraceptives Oral |
| Zdroj: | European journal of clinical pharmacology. 47(5) |
| ISSN: | 0031-6970 |
| Popis: | CYP1A2 is a cytochrome P450 which is inducible by polycyclic aromatic hydrocarbons. This induction could be mediated via the Ah locus, which encodes a cytosolic receptor responsible for the regulation of the CYP1A1 gene. Enzyme activity in vivo can be measured by the urinary caffeine metabolite ratio (AFMU + 1X + 1U)/17U. Our goal was to determine, using this ratio, the possible existence of a genetic polymorphism in CYP1A2 induction. For this purpose, a population and family study, including smokers, were undertaken. In a first step, we investigated factors influencing enzyme activity in a population of 245 unrelated individuals. The induction effect of smoking and inhibiting effect of oral contraceptive use were confirmed. None of the other factors examined (age, sex, level of cigarette consumption, nicotine or tar amounts, filter, inhalation) accounted for the interindividual variability in the metabolic ratio. Using the statistical SKUMIX method, a unimodal (one peak) distribution of the ratio was concluded in 164 unrelated smokers, since a second distribution did not significantly improve the fit to the data (chi 2(1) = 1.39, P > 0.2). Segregation analysis was performed on 68 nuclear families and no major gene effect could be shown. Furthermore, the polygenic model did not provide a higher likelihood than the sporadic one, which argues against the existence of any familial resemblance. Although we cannot rule out the possibility that some environmental factors could obscure the phenotypes and occult a genetic determinism, we conclude that genetic factors are probably negligible in the determination of CYP1A2 activity measured by this method.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: | OpenAIRE |
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