This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The protein encoded by this gene localizes to the endoplasmic reticulum and its expression is induced by some polycyclic aromatic hydrocarbons (PAHs), some of which are found in cigarette smoke. The enzyme’s endogenous substrate is unknown; however, it is able to metabolize some PAHs to carcinogenic intermediates. Other xenobiotic substrates for this enzyme include caffeine, aflatoxin B1, and acetaminophen.CYP1A2 also metabolizes many medications, including theophylline, diazepam, caffeine, many antidepressants, and antipsychotics. CYP1A2 enzymatic activity can be induced by several medications, substrates, and constituents of tobacco smoke. CYP1A2 can also be inhibited by several medications. Detecting inherited variants of the CYP1A2 gene that cause altered enzymatic activity, particularly in the presence of an inducer, can identify patients who may be at increased risk of having adverse drug reactions or therapeutic failure to standard dosages of CYP1A2 medications.
CYP1A2 master drug list
PSYCHIATRY: Olanzapine, Clozapine, Imipramine, Clomipramine, Mirtazapine, Bupropion, Promazine, Asenapine, Zyprexa, Clozaril. Tofranil, Anafranil, Remeron, Wellbutrin, Cymbalta, Sparine. Saphris
OTHER DRUGS: Lidocaine, Ropivicaine, theophylline, zolmipitran, triamterene, flutamide, tizanidine, tacrine, 17 beta estradiol, zomig, eulexin etc.
The enzyme produced by this gene is responsible for about 95% of all caffeine metabolisation in the body. As with all our genes, there are two different alleles, in this case A and C. The A allele is associated with a higher activity of the CYP1A2 enzyme, and the C allele is associated with lower activity of the enzyme. With regards to caffeine response, AA genotypes tend to metabolise caffeine quicker than AC and CC genotypes – as a result AA genotypes are called “fast metabolisers” and the AC and CC genotypes are classed as “slow metabolisers”. This can be important, because research has looked at the effects of caffeine on cardiovascular health, and have found that the effect of caffeine differs between genotypes. In a 2006 study it was found that if slow metabolisers had more than about 3 cups of coffee per day, their risk of suffering from a myocardial infarction was much increased. However, this effect was not found in fast metabolisers. An other study from 2009 study found that higher amounts of caffeine (approximately 3 cups of coffee per day) were associated with an increased risk of hypertension – but only in slow caffeine metabolizers. Based on these studies is recommended that slow metabolizers should limit their intake of caffeine to around 200mg per day, counting all sources of caffeine not just coffee
Fast metabolizers can consume more caffeine should they wish, up to approximately 300mg per day.
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