Details

Autor(en) / Beteiligte

• Matthaei, J
• Tzvetkov, MV
• Strube, J
• Sehrt, D
• Sachse-Seeboth, C
• Hjelmborg, JB
• Möller, S
• Halekoh, U
• Hofmann, U
• Schwab, M
• Kerb, R
• Brockmöller, J

Titel

Heritability of Caffeine Metabolism: Environmental Effects Masking Genetic Effects on CYP1A2 Activity but Not on NAT2

Ist Teil von

• Clinical pharmacology and therapeutics, 2016-12, Vol.100 (6), p.606-616

Ort / Verlag

United States: Blackwell Publishing Ltd

Erscheinungsjahr

2016

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• 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.