Heritability of caffeine metabolism:Environmental effects masking genetic effects on CYP1A2 activity but not on NAT2
| Autor: | Matthaei, Johannes, Tzvetkov, Mladen V, Strube, Jakob, Sehrt, Daniel, Sachse-Seeboth, Cordula, Hjelmborg, Jacob v. B., Möller, Sören, Halekoh, Ulrich, Hofmann, Ute, Schwab, Matthias, Kerb, Reinhold, Brockmöller, Jürgen |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
Adult Adolescent Arylamine N-Acetyltransferase CYP1A2 Arylamine N-Acetyltransferase/genetics Smoking/metabolism Twins Monozygotic/genetics heritability Environment Twins Dizygotic/genetics Young Adult Cytochrome P-450 CYP1A2/genetics Cytochrome P-450 CYP1A2 Caffeine Humans twin study Polymorphism Genetic Cytochrome P-450 CYP1A1/genetics Middle Aged NAT2 Contraceptives Oral Hormonal/administration & dosage Caffeine/metabolism Pharmacogenetics Area Under Curve twin Female |
| Zdroj: | Matthaei, J, Tzvetkov, M V, Strube, J, Sehrt, D, Sachse-Seeboth, C, Hjelmborg, J V B, Möller, S, Halekoh, U, Hofmann, U, Schwab, M, Kerb, R & Brockmöller, J 2016, ' Heritability of caffeine metabolism : Environmental effects masking genetic effects on CYP1A2 activity but not on NAT2 ', Clinical Pharmacology & Therapeutics, vol. 100, no. 6, pp. 606-616 . https://doi.org/10.1002/cpt.444 |
| DOI: | 10.1002/cpt.444 |
| Popis: | Heritability of caffeine pharmacokinetics and cytochrome P450 1A2 (CYP1A2) activity is controversial. Here, we analyzed the pharmacokinetics of caffeine, an in vivo probe drug for CYP1A2 and arylamine N-acetyltransferase 2 (NAT2) activity, in monozygotic (MZ) and dizygotic (DZ) twins. In the entire group, common and unique environmental effects explained most variation in caffeine area under the curve (AUC). Apparently, smoking and hormonal contraceptives masked the genetic effects on CYP1A2 activity. However, when excluding smokers and users of hormonal contraceptives, 89% of caffeine AUC variation was due to genetic effects and, even in the entire group, 8% of caffeine AUC variation could be explained by a CYP1A1/1A2 promotor polymorphism (rs2470893). In contrast, nearly all of the variations (99%) of NAT2 activity were explained by genetic effects. This study illustrates two very different situations in pharmacogenetics from an almost exclusively genetic determination of NAT2 activity with no environmental modulation to only moderate genetic effects on CYP1A2 activity with strong environmental modulation. |
| Databáze: | OpenAIRE |
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