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Talk:CYP1A2

From SNPedia

The text on the first page of CYP1A2 F calls it the fast allele. My reading of the literature suggests the opposite.

(CYP1A2*1F) in the CYP1A2 gene decreases enzyme inducibility as measured by plasma or urinary [caffeine]/[caffeine metabolite] ratio after a dose of caffeine ( http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2474926/ ) CYP1A2*1A allele are "rapid" caffeine metabolizers, whereas carriers of the variant CYP1A2*1F are "slow" caffeine metabolizers. Examiner.com In this case, carriers of the CYP1A2*1F allele are slow metabolizers of caffeine, whereas individuals who are homozygous for the CYP1A2*1A allele are rapid caffeine metabolizers, he said. medscape.com The rs762551(A) allele is the "fast metabolizer" allele known as CYP1A2*1F; the (C) allele is by comparison a slower metabolizer of certain substrates (including caffeine). The CYP1A2*1F allele which is quite common (40 to 50%) is due to a substitution of a base in the non-coding region of the CYP1A2 gene and has the effect of decreasing the enzyme inducibility. Individuals who are homozygous for the CYP1A2*1F allele are 'slow' caffeine metabolizers. Thus for these individual increased intake of caffeine seems to be associated with a concomitant increase in the risk of non-fatal myocardial infraction (MI). http://www.uniprot.org/uniprot/P05177

Individuals who are homozygous for the CYP1A2*1A allele are "rapid" caffeine metabolizers, whereas carriers of the variant CYP1A2*1F are "slow" caffeine metabolizers. http://www.ncbi.nlm.nih.gov/pubmed/16522833 These data show that the risk of hypertension associated with coffee intake varies according to CYP1A2 genotype. Carriers of slow *1F allele are at increased risk and should thus abstain from coffee, whereas individuals with *1A/*1A genotype can safely drink coffee. http://www.ncbi.nlm.nih.gov/pubmed/19451835 Caffeine metabolism: Individuals who are homozygous for the CYP1A2*1A allele are "rapid" caffeine metabolizers, whereas carriers of the variant CYP1A2*1F are "slow" caffeine metabolizers.

Caffeine "Individuals who are homozygous for the CYP1A2*1A allele are "rapid" caffeine metabolizers, whereas carriers of the variant CYP1A2*1F are "slow" caffeine metabolizers." http://www.ncbi.nlm.nih.gov/pubmed/16522833

Individuals who have two copies of the fast CYP1A2*1A allele are fast caffeine metabolizers; whereas people who have at least one copy of the slow CYP1A2*1F allele are slow caffeine metabolizers. amerturksgenetics.com "Carriers of the gene variant *1F allele are slow caffeine metabolizers, whereas individuals homozygous for the *1A/*1A genotype are rapid caffeine metabolizers." http://www.examiner.com/article/are-you-a-slow-or-fast-metabolizer-of-caffeine-how-does-this-affect-your-health "Individuals who are homozygous for the CYP1A2*1A allele (A/A) are “rapid” caffeine metabolizers whereas carriers of the variant CYP1A2*1F are “slow” caffeine metabolizers." http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2474926/


Response
This is definitely a confusing topic, due to the lack of agreement in the literature over whether the *1F allele is defined by rs762551(A), or, rs762551(C). In general, the publications that designate the *1F allele as being defined by rs762551(C) conclude it is a slow metabolizing allele, whereas the publications that define the *1F allele as rs762551(A) conclude it is a fast (or ultrafast) metabolizing allele. Basically this means the publications agree on which SNP is the "fast one" - it is rs762551(A) - but they disagree on which allele gets to be called *1F.
In SNPedia, we are following the convention of the major CYP database, the Human CYP Allele Nomenclature Database at URL http://www.cypalleles.ki.se/ in designating the rs762551(A) allele as *1F. This is also in agreement with PharmGKB (see this page) as well as the explanation outlined in the 1F discussion from the relatively recent (2012) CYP1A2 review found [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3346273/#S5title here. Last and least, we note that our designation is also consistent with how 23andMe describes these genotypes, even though they only cite the 2006 paper that you also do, which is one of the papers that flips which allele is *1F.
In summary, while it is quite confusing, the way that the rs762551 genotypes are assigned fast vs slow metabolizer status in SNPedia appears to us to be both correct and consistent with current nomenclature.Greg (talk) 22:12, 13 May 2014 (UTC)