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Influence of Environmental and Genetic Factors on CYP1A2 Activity in Individuals of South Asian and European Ancestry
Author(s) -
Perera V,
Gross A S,
McLachlan A J
Publication year - 2012
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.2012.139
Subject(s) - paraxanthine , caffeine , cyp1a2 , population , medicine , pharmacogenetics , physiology , biology , genetics , genotype , environmental health , metabolism , gene , cytochrome p450
The drug‐metabolizing enzyme CYP1A2 contributes to the metabolism of a number of commonly used medicines and displays wide interindividual variability. The aim of this study was to investigate CYP1A2 activity in a population of South Asian ancestry and compare it with a population of European ancestry. CYP1A2 activity was determined using the 4 h paraxanthine/caffeine saliva concentration ratio following a 100‐mg oral dose of caffeine in healthy individuals of South Asian ( n = 166) and European ( n = 166) ancestry. Participants were surveyed for extrinsic ethnic factors and genotyped for polymorphisms in CYP1A2 and related genes. Significantly lower CYP1A2 activity was observed in South Asian participants (median: 0.42; range: 0.10–1.06) as compared with European participants (0.54; 0.12–1.64) ( P < 0.01). Multiple linear regression indicated that 41% of the variability in CYP1A2 activity could be explained by the diet, lifestyle, and genetic factors studied. Clinical Pharmacology & Therapeutics (2012); 92 4, 511–519. doi: 10.1038/clpt.2012.139