In previous issues of Pharmacy Times we have discussed the cytochrome P450 (CYP450) enzymes CYP1A2, CYP2C9, and CYP2C19. If you are heterozygous, A/C at the CYP1A2 gene you would be considered “wild type”, what the general population carries, and a normal metabolizer. A meta-analysis looked at the association between habitual coffee intake and CYP1A2 polymorphism that splits the population into fast caffeine metabolisers and slow caffeine metabolisers 43 . Caffeine is metabolized in the body by the enzyme Cytochrome P450 1A2 (CYP1A2) in the liver. In this issue, we will discuss CYP2D6?an enzyme that is involved in the metabolism of numerous drugs. [ PMID 16413245] . You may be a fast metabolizer of the caffeine, you may be a slow metabolizer of the extra epinephrine and norepinephrine that the caffeine helped release. We have a liver enzyme that is responsible for metabolizing caffeine (CYP1A2). If you are A/A homozygous at the CYP1A2 gene you would be considered a fast metabolizer of certain drugs as well as caffeine. In the mid-1980s, slow and fast metabolizer phenotypes were reported based on the metabolism of the chemical carcinogen acetylaminofluorene in a panel of human liver microsomal preparations. The C allele is considered the wild-type, even though it is the rarer allele in most populations. CC, AC = CYP1A2*1C = Slow Metabolizer. March 5, 2018 Shari Basch. Researchers have discovered a caffeine gene that regulates whether people are slow or fast metabolizers of caffeine. About 5 out of 100 people have this gene status. 'Performance' dips in 1 in 10 of us. Alternatively, some drugs such as Plavix convert into their active drug state through CYP2C19. And for those of you who are also interested in the technical aspects, the relevant genes are the AHR and CYP1A2 genes. Intermediate Metabolizer: An intermediate-metabolizing enzyme is considered to be less active. The function of this CYP will likely be diminished to such a degree that the person will convert from an Intermediate Metabolizer into a Poor Metabolizer. This gene encodes a member of the cytochrome P450 superfamily of enzymes. Apparently, there is an enzyme in the liver that metabolizes caffeine, p450 1A2 (CYP1A2) and it works differently in different people. Certain drugs should be used with caution and patients may need to have their doses of some medications adjusted. CYP1A2 is part of the cytochrome P450 (CYP) family of drug metabolizing enzymes. People with one or two copies of CYP1A2 (a.k.a. CYP1A2 I wonder if the slow-metabolisers of a cup of coffee (caffeine) know who they are? A genetic test can tell you whether you’re a slow or fast metabolizer and it’s currently available. This CYP has only one functioning allele, which is inhibited by citalopram. How Being a Poor, Intermediate, Rapid, or Ultra Rapid Metabolizer can Impact Your Medication Outcomes. To minimize mold, use single estate and/or single origin beans for your coffee. The CYP1A2 gene encodes a member of the cytochrome p450 family of proteins, which metabolize nutrients and drugs. Increased risk of heart attack by 36%. The CYP1A2 gene encodes a member of the cytochrome p450 family of proteins, which metabolize nutrients and drugs. Therefore, you may be a fast or slow caffeine metabolizer based on your CYP1A2 genetics. A polymorphism of the gene coding for CYP1A2, the enzyme responsible for 95% of caffeine metabolism, may potentially divide the population into ‘slow’ and ‘fast’ caffeine metabolisers 16,17. extensive metabolizer – normal CYP2D6 function ultrarapid metabolizer – multiple copies of the CYP2D6 gene are expressed, so greater-than-normal CYP2D6 function occurs A patient's CYP2D6 phenotype is often clinically determined via the administration of debrisoquine (a selective CYP2D6 substrate) and subsequent plasma concentration assay of the debrisoquine metabolite (4-hydroxydebrisoquine). This explains why some people can drink more coffee or tea than others. Bonus Tip: Mold in coffee can also cause excitability in those who are sensitive. Using the metabolism of caffeine as a marker of activity in vivo, several investigators demonstrated high interindividual and interethnic variability in CYP1A2 activity. * However, bear in mind that the lethal dose is 2 grams of caffeine per day. kg in those with the CC genotype. Let’s look at CYP1A2 in table 4. ... 18850169] but this is still an over-simplification since as mentioned above the fast metabolizer phenotype for rs762551AA is only observed under induction by smoking or high habitual coffee intake. If you are a fast metabolizer (with an ‘AA’ genotype), you are unlikely to get nervous or anxious after drinking coffee [R].You are also more likely to benefit from caffeine as an athletic performance booster [R]!But more importantly, drinking coffee may actually protect you against developing high blood pressure (hypertension) and heart disease [R, R]. This gene comes in two versions, according to Nature. The CYP1A2 gene controls the activity of the cytochrome P450 1A2 enzyme, which is responsible for nearly all of our metabolic processing of caffeine. Now what? A variant at the CYP1A2 gene can determine whether an individual is a fast or slow metabolizer of caffeine, and this has some effect on the blood pressure and cardiovascular health of an individual. Consider this case: Two patients each take the same dose of the same antidepressant medication. AA = CYP1A2*1F = Fast Metabolizer. The information obtained from the genetic testing allowed my specialist to tailor medication doses to my metabolism, allowing me to use drugs we had previously thought I could not tolerate. Slow metabolizers have a greater risk for hypertension and heart attack when they drink more than 2 cups per day on a regular basis. Turns out I am a poor metabolizer for 2D6, which explained my adverse reactions to the Beta blockers and tricyclic antidepressants. 2-3 cups (300 mg)/day. This results in very high CYP2C19 activity. Once on the search results page, find the rs762551 SNP. For example, if a particular CYP450 variation makes someone a rapid metabolizer of a drug, he or she may process it so fast that the drug won’t have a chance to reach optimal blood levels, leading to limited amounts of drug that can act on the patient’s system. Metabolizer Phenotype Enzyme Activity ; Normal Metabolizer: A normal-metabolizing enzyme may generally break down standard doses of a drug. According Cornelis et al. On the other hand, cancer patients who are CYP2C19*17 carriers are more likely to benefit from tamoxifen treatment, … I have the results of my patient’s CYP1A2 test. Two variants of the gene exist: the CPA1A2*1A allele results in fast caffeine metabolism, while the CPA1A2*1F allele results in slower caffeine metabolism. CYP1A2 is the key liver enzyme (special proteins that breakdown and use other substances) responsible for metabolizing caffeine. If you’ve done 23andme, log in, go to “My account,” select “Browse raw data,” and type “CYP1A2” into the “Jump to a gene” search box. However, for the fast metabolizers, coffee correlated with a lower risk for heart attacks. Variations in the CYP1A2 gene have a big impact on how caffeine affects our bodies. It codes for an enzyme that helps break down caffeine. CYP1A2 genotype should be considered when deciding whether … One well known substrate of CYP1A2 is caffeine; individuals who carry one or more CYP1A2*1C alleles are "slow" caffeine metabolizers, whereas carriers of the variant CYP1A2*1F are "fast" caffeine metabolizers.The same amount of caffeine will therefore tend to have … Thirty-seven participants (19-50 years old) took place in the study and were categorized according to i) genotype: CYP1A2 (AA) "fast metabolizer", and CYP1A2 (AC) "slow metabolizer"; ii) physical activity level: sedentary (S) and physically active (A); and iii) caffeine consumption level: non-habitual caffeine consumer (NC) and habitual heavy caffeine consumer (C). If you can drink coffee without feeling any jittery feelings, you are a fast metabolizer and … Ultrarapid metabolizer – multiple copies of the CYP2D6 gene are expressed, and therefore greater-than-normal CYP2D6 function. One well known substrate of CYP1A2 is caffeine. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. The Bottom Line Based on the available research, coffee seems to have health benefits and may even lower the risk of heart disease – but this isn’t universally the case. This protein localizes to the endoplasmic reticulum and hydroxylates steroids at the 21 position. Does not increase heart attack risk. Patients m51 and m52 have a CYP2D6 gene duplication; patients m46 and m50 do not carry duplicate genes.Lanes 2–5 show the results of DNA amplification using primer pair cyp-17f/cyp-32r in samples m46, m50, m51, and m52, successively. I have found a test you can do to find out whether you are a fast or slow caffeine metabolizer by 23andme but I need to do a bit more research on whether they send the test kits to … (10-12) Risks/Benefits for SLOW metabolizers. CYP2D6 also is involved in the activation of some drugs, so these drugs may have reduced efficacy when patients with inadequate CYP2D6 activity take them. Therefore, caffeine will be metabolized (broken down) faster in a smoker than a non-smoker, which can lead the person to feel that the caffeine did not have much of an effect on their body. In my genotype, *2xN the N stands for the number of alleles and could be anywhere from 2 copies up to 13 (that they know of.) the “slow” gene) metabolize caffeine slowly, while people carrying one or two copies of the “fast… a person who is a fast metabolizer of caffeine can drink up to 6 cups of coffee a day and have no effects. The gene also plays a role in regulating an infant’s weight during the pregnancy of a woman, and this has a link with caffeine intake. There are more technical explanations of course. Get your genetic test from 23andMe: https://refer.23andme.com/s/wgt3f Important studies mentioned in video: 1. CYP1A2 is a gene. rs12248560(T) defines the CYP2C19*17 allele, an ultra fast metabolizer phenotype of the CYP2C19 gene.. CYP2C19*17 is likely to lead to less effective drug treatment by, for example, proton pump inhibitors (such as omeprazole) and antidepressants. A fast metabolizer taking omeprazole (Prilosec) to treat h. pylori may have an insufficient response because the drug may not remain active in the body long enough. 1-2 cups (200 mg)/day. Long-PCR assays for detection of alleles with duplicate CYP2D6 genes.. For example, smoking will induce CYP1A2, which will speed up the metabolism of caffeine. Homozygous CYP1A2*1A - Fast Metabolizer; Risks/Benefits. Fast Metabolizers. Caffeine Intake Amount. Ultrarapid Metabolizer (UM) – This means there are two copies of a CYP2C19 gene with increased activity. 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