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Genetics - Cytochrome P450 1A2 Induced by smoking tobacco...

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Cytochrome P450 1A2 Induced by smoking tobacco Catalyzes primary metabolism of: o Theophylline o Imipramine o Propranolol o Clozapine Inhibited by: o Many fluoroquinolone antibiotics o Fluvoxamine o Cimetidine Frequent genetic polymorphisms in CYP21A2 affect therapeutic response to drugs. The enzyme activity is expressed at highly variable levels. Three phenotypes are identified: normal induction, diminished induction and hyperinduction. Genetic polymorphisms in the CYP1A2 gene influence the magnitude of CYP1A2 induction. Two important polymorphisms that cause functional changes in enzymatic activity have been identified in the CYP1A2*1 the wild-type allele. The CYP1A2*1C allele is the result of a single point mutation (-3860 G>A) and is associated with decreased CYP1A2 metabolic activity in comparison to the normal wild-type CYP1A2*1A allele. The CYP1A2*1F allele is the result of a single point mutation (- 163 C>A) and is associated with increased induction particularly in smokers in comparison to the wild-type CYP1A2*1A allele. The
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