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CYP2A6 genotype and toxicity of nicotine in never smokers
Author(s) -
Dempsey D. A.,
Jacob P.,
Tyndale R. F.,
Hoffmann E.,
Benowitz N. L.
Publication year - 2005
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 - 10.1016/j.clpt.2004.11.020
Subject(s) - cyp2a6 , nicotine , lightheadedness , medicine , clinical pharmacology , genotype , nausea , pharmacology , physiology , genetics , biology , metabolism , cytochrome p450 , cyp1a2 , gene
Background/Aims To examine genetic factors that influence sensitivity to nicotine (Nic) in never smokers. Methods 20 Caucasian and 20 Asian never smokers received 7 mg nicotine skin patches, with frequent blood levels, subjective and cardiovascular (CV) effect monitoring. CYP2A6, the enzyme primarily responsible for Nic metabolism, was genotyped. Results 25 subjects had wild type alleles (*1A and/or*1B) for CYP2A6, while 15 subjects had CYP2A6 variant alleles (*4,*9,*10) which are associated with slower Nic metabolism (Var‐2A6). 8 subjects vomited, of whom 75% had Var‐2A6 compared to 25% in those who did not (p<0.02). Nic levels (AUC 0–90min) were significantly higher in those who vomited. Var‐2A6 subjects had more adverse responses to Nic including reduced alertness, concentration and contentedness, and, more lightheadedness and nausea (all p<0.05). CV responses did not differ by genotype. Conclusions Variant CYP2A6 (*4,*9,*10) genotype is associated with more toxicity from Nic in never smokers. Genotype could influence responses to the first cigarette in never smokers and responses to Nic medications used to treat Nic addiction. Clinical Pharmacology & Therapeutics (2005) 77 , P4–P4; doi: 10.1016/j.clpt.2004.11.020