How can I find out what version of CYP1A2 I have?

Genetics as it applies to evolution, molecular biology, and medical aspects.

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How can I find out what version of CYP1A2 I have?

Post by gstevenz » Fri Feb 24, 2012 12:30 am, lists a range of, it would appear, empirically validated health benefits of coffee including : Reduced risk of Alzheimer's disease and dementia, reduced risk of gallstone disease, reduced risk of Parkinson's disease, improved cognitive performance, analgesic enhancement, risk of diabetes mellitus type 2 by up to half, liver protection, a reduced risk of oral, esophageal, and pharyngeal cancer, a lower risk of aggressive prostate cancer, cardioprotection, antioxidation, prevention of dental caries and a decreased risk of gout in men over age 40.

Unfortunately, it also states that;

Polymorphisms in the CYP1A2 gene may lead to a slower metabolism of caffeine. In patients with a slow version of the enzyme the risk for myocardial infarction (heart attack) is increased by a third (2–3 cups) to two thirds (>4 cups). The risk was more marked in people under the age of 59.

[Cornelis MC, El-Sohemy A, Kabagambe EK, Campos H (March 2006). "Coffee, CYP1A2 Genotype, and Risk of Myocardial Infarction"JAMA: the Journal of the American Medical Association 295 (10): 1135–41. doi:10.1001/jama.295.10.1135. PMID 16522833], states that "The CYP1A2 gene encodes a member of the cytochrome p450 family of proteins, which metabolize nutrients and drugs. One well known substrate of CYP1A2 is caffeine; individuals who are carry one or more CYP1A2*1C alleles are "slow" caffeine metabolizers, whereas carriers of the variant CYP1A2*1F are "fast" caffeine metabolizers."

I should like to know therefore, how it might be possible for me to discover which of these two categories I fall into.

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Post by AstraSequi » Fri Feb 24, 2012 7:41 am

1. You could find a company that offers SNP genotyping, like 23andMe, and then check to make sure that they test for that specific polymorphism. This will also give you information about a lot of different polymorphisms as well.

2. Or, if you're only interested in the one polymorphism, and you have access to a biological lab, you could also take a sample of your cheek cells and PCR the gene out of your DNA. I would use the same idea that is used for BRCA mutation identification - two forward primers where the 3`-most nucleotide is the one that is different in the polymorphism. Only the primer corresponding to your variation will be able to amplify (the other will have a mismatch at the 3` end, and the polymerase won't be able to extend). I think this would be the cheapest (other than perhaps #4), though probably the most time-consuming.

3. You could also spend a few thousand dollars and sequence your entire genome. :) (Or wait a few years until the cost is much lower, and sequence it then - depending on how much value you put on having the information soon. I think the SNP genotyping would also drop in price over the same timeframe.)

4. Finally, you could probably do some test of caffeine metabolism directly. I'm not sure how you might do this, but you could drink a defined amount of caffeine, wait for a defined time interval, and then measure the level of caffeine or caffeine byproducts in your blood. I would probably want several timepoints to be sure ofthe results (they should show an exponential decrease, which you could use to graph an equation, and the coefficients of the equation would tell you the answer). This would have the advantage of telling you exactly how fast you metabolize caffeine (within the margin of error - which, of course, you can reduce by doing replicates), including any effects on caffeine metabolism by genes other than CYP1A2. I would add a caveat, though, that if you don't already consume caffeine regularly, you're likely to have some degree of metabolic adaptation occur - so the results you get might change after your first few weeks or months.

I hope that helps!

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