Talk:Rs762551

From the opening description, it seems to say that the major A allele is the *1F allele using star nomenclature ("The rs762551(A) allele is the "fast metabolizer" allele known as CYP1A2*1F"). But the major A/A is classified as 1A. A/C or CC is *1F Reference: PMID# 10233211, 16522833 seems most of the existing language was derived from the Jernström paper (PMID: 18813311) that is riddled with typographic errors.

Common nomenclature errors and misinterpretations of SNPs at Rs762551

There is an error concerning the designation of 'fast' and 'slow' caffeine metabolizers in the description for this particular SNP.

Sources indicate that there has been a gross mis-classification in the literature between the *1A and the *1F genotypes and its effects on caffeine metabolism by CYP1A2 (See: 10.1001/jama.296.7.764-b and 10.1097/FPC.0b013e32835ccc76 for a discussion of this). In short, there are no 'slow' or 'fast' metabolizers of caffeine as with SNPs in Rs762551, but rather different SNPs in this region are inducible under the influence of various drugs and environmental conditions. In this case, the A/A genotype is inducible with smoking and omeprazole while the C/C genotype is not. There is no evidence in the literature to suggest that the rates at which CYP1A2 metabolizes caffeine at a baseline level (with no induction by smoking or otherwise) is affected by the different SNPs at Rs762551.

The SNP concerning caffeine metabolism was first identified in the literature as -163 C>A at region Rs762551 in which the authors showed that the A/A genotype had increased CYP1A2 enzyme activity on caffeine in smokers (see: 10.1046/j.1365-2125.1999.00898.x). These authors originally chose the more highly inducible form (A/A) to be designated as CYP1A2*1A. However, in 1999 the Human Cytochrome P450 Nomenclature Committee was formed which subsequently designated the A/A inducible form (A/A) as CYP1A2 *1F and the wildtype (C/C) as CYP1A2*1A. As such, confusion in the literature has evolved depending on which convention was used (10.1001/jama.296.7.764-b and 10.1097/FPC.0b013e32835ccc76), especially since the wild type (C/C) is more rare than its counterpart.

It needs to be emphasized again that the alteration in inducibility by foreign substances (i.e., smoking) between SNPs at rs762551 has absolutely nothing to do with the baseline levels (slow vs. fast) of CYP1A2 activity. Furthermore, several studies linked within the SNPedia Rs762551 have incorrectly identified the *1A and *1F variants with their incorrect SNPs and as such, caution should be taken in extrapolating results from these studies.

Refs. as DOI's: 10.1001/jama.296.7.764-b 10.1097/FPC.0b013e32835ccc76 10.1046/j.1365-2125.1999.00898.x