CYP1A2 is the key liver enzyme (special proteins that breakdown and use other substances) responsible for metabolizing caffeine. 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 . In the far right column, it will give your variant of that SNP. A genetic test can tell you whether you’re a slow or fast metabolizer and it’s currently available. Risks/Benefits for SLOW metabolizers. 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. 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]. Turns out I am a poor metabolizer for 2D6, which explained my adverse reactions to the Beta blockers and tricyclic antidepressants. [ PMID 16413245] . Certain drugs should be used with caution and patients may need to have their doses of some medications adjusted. 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). About 5 out of 100 people have this gene status. It codes for an enzyme that helps break down caffeine. (10-12) 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 … 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. 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. This explains why some people can drink more coffee or tea than others. ... 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. Homozygous CYP1A2*1A - Fast Metabolizer; Risks/Benefits. 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). In this issue, we will discuss CYP2D6?an enzyme that is involved in the metabolism of numerous drugs. 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 results in very high CYP2C19 activity. The gene, known as CYP1A2, is also used by genetic testing firms to predict a person's risk of nonfatal heart attack. Researchers have discovered a caffeine gene that regulates whether people are slow or fast metabolizers of caffeine. Fast Metabolizers. The CYP1A2 gene controls the activity of the cytochrome P450 1A2 enzyme, which is responsible for nearly all of our metabolic processing of caffeine. According Cornelis et al. 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. Ultrarapid Metabolizer (UM) – This means there are two copies of a CYP2C19 gene with increased activity. This gene comes in two versions, according to Nature. 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. CYP1A2 I wonder if the slow-metabolisers of a cup of coffee (caffeine) know who they are? Metabolizer Phenotype Enzyme Activity ; Normal Metabolizer: A normal-metabolizing enzyme may generally break down standard doses of a drug. CYP1A2 is a gene. The C allele is considered the wild-type, even though it is the rarer allele in most populations. Let’s look at CYP1A2 in table 4. 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 … I have the results of my patient’s CYP1A2 test. March 5, 2018 Shari Basch. AA = CYP1A2*1F = Fast Metabolizer. And for those of you who are also interested in the technical aspects, the relevant genes are the AHR and CYP1A2 genes. For example, smoking will induce CYP1A2, which will speed up the metabolism of caffeine. CYP1A2 is part of the cytochrome P450 (CYP) family of drug metabolizing enzymes. The CYP1A2 gene encodes a member of the cytochrome p450 family of proteins, which metabolize nutrients and drugs. 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. Does not increase heart attack risk. The CYP1A2 gene encodes a member of the cytochrome p450 family of proteins, which metabolize nutrients and drugs. This CYP has only one functioning allele, which is inhibited by citalopram. Long-PCR assays for detection of alleles with duplicate CYP2D6 genes.. Increased risk of heart attack by 36%. Slow metabolizers have a greater risk for hypertension and heart attack when they drink more than 2 cups per day on a regular basis. 1-2 cups (200 mg)/day. How Being a Poor, Intermediate, Rapid, or Ultra Rapid Metabolizer can Impact Your Medication Outcomes. the “slow” gene) metabolize caffeine slowly, while people carrying one or two copies of the “fast… We have a liver enzyme that is responsible for metabolizing caffeine (CYP1A2). 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. For CYP2D6 and CYP3A4, similar problems arise concerning Citalopram. There are more technical explanations of course. Alternatively, some drugs such as Plavix convert into their active drug state through CYP2C19. 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. Apparently, there is an enzyme in the liver that metabolizes caffeine, p450 1A2 (CYP1A2) and it works differently in different people. Variations in the CYP1A2 gene have a big impact on how caffeine affects our bodies. It doesn't break down a drug as completely as a normal metabolizer, which means you might require a lower dose. Get your genetic test from 23andMe: https://refer.23andme.com/s/wgt3f Important studies mentioned in video: 1. 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. 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. 'Performance' dips in 1 in 10 of us. People with one or two copies of CYP1A2 (a.k.a. However, bear in mind that the lethal dose is 2 grams of caffeine per day. Bonus Tip: Mold in coffee can also cause excitability in those who are sensitive. Therefore, you may be a fast or slow caffeine metabolizer based on your CYP1A2 genetics. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. I needed about 1/4 the dose of a “normal” person. 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.) kg in those with the CC genotype. Intermediate Metabolizer: An intermediate-metabolizing enzyme is considered to be less active. One well known substrate of CYP1A2 is caffeine. Once on the search results page, find the rs762551 SNP. This protein localizes to the endoplasmic reticulum and hydroxylates steroids at the 21 position. 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. Ultrarapid metabolizer – multiple copies of the CYP2D6 gene are expressed, and therefore greater-than-normal CYP2D6 function. Consider this case: Two patients each take the same dose of the same antidepressant medication. 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. Caffeine is metabolized in the body by the enzyme Cytochrome P450 1A2 (CYP1A2) in the liver. Using the metabolism of caffeine as a marker of activity in vivo, several investigators demonstrated high interindividual and interethnic variability in CYP1A2 activity. 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 gene encodes a member of the cytochrome P450 superfamily of enzymes. 2-3 cups (300 mg)/day. However, for the fast metabolizers, coffee correlated with a lower risk for heart attacks. 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. Your genes determine if you are a 'fast' caffeine metabolizer who can drink 4 cups of coffee per day without a problem or a 'slow' caffeine metabolizer who can't handle more than one cup. CYP1A2 genotype should be considered when deciding whether … 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. Caffeine Intake Amount. 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. a person who is a fast metabolizer of caffeine can drink up to 6 cups of coffee a day and have no effects. 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 previous issues of Pharmacy Times we have discussed the cytochrome P450 (CYP450) enzymes CYP1A2, CYP2C9, and CYP2C19. CC, AC = CYP1A2*1C = Slow Metabolizer. * If you are AA, you’re a fast metabolizer. To minimize mold, use single estate and/or single origin beans for your coffee. On the other hand, cancer patients who are CYP2C19*17 carriers are more likely to benefit from tamoxifen treatment, … Now what? 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