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Here, we analyzed the pharmacokinetics of caffeine, an <jats:italic>in vivo<\/jats:italic> probe drug for CYP1A2 and arylamine N\u2010acetyltransferase 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.<\/jats:p>","DOI":"10.1002\/cpt.444","type":"journal-article","created":{"date-parts":[[2016,8,10]],"date-time":"2016-08-10T14:16:42Z","timestamp":1470838602000},"page":"606-616","source":"Crossref","is-referenced-by-count":36,"title":["Heritability of Caffeine Metabolism: Environmental Effects Masking Genetic Effects on CYP1A2 Activity but Not on NAT2"],"prefix":"10.1111","volume":"100","author":[{"given":"J","family":"Matthaei","sequence":"first","affiliation":[{"name":"Institute for Clinical Pharmacology, University Medical Center, G\u00f6ttingen Georg\u2010August University G\u00f6ttingen 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