CYP1A2 * 1F (rs762551)

Coffee is a major source of caffeine (1,3,7 - trimethylxanthine), which is the most consumed stimulant in the world and has been implicated in the development of cardiovascular diseases such as acute myocardial infarction. Caffeine is metabolized in the liver, primarily by cytochrome P450 1A2 (CYP1A2), which is involved in about 95% of the caffeine metabolism and shows a wide variability of enzyme activity between individuals. The only genetic factors may explain 35-75% of the variation observed in activity of the enzyme CYP1A2. A → C substitution in position -163, within non-coding exon 1 of gene CYP1A2 decreases the activity of the enzyme, resulting in impaired metabolism of caffeine.

The subjects with the genotype CC or CA are metabolizers "slow" (or "poor") of caffeine, while individuals who are homozygous for the allele AA are metabolizers "rapid" (or "fast") of caffeine. Individuals "CYP1A2 * 1F" are considered "fast" metabolizers of caffeine. There is confusion about the definition of CYP1A2 * 1F allele in the literature. According to the Human CYP-allele Nomenclature Committee individuals classified CYP1A2 * 1F are considered carriers of allele -163A. The C allele was associated with an increased cardiovascular risk, due to decreased metabolism of caffeine, in the event of excessive consumption of coffee. This SNP is the best studied genetic variant CYP1A2. It is the only variant of haplotype CYP1A2 * 1F and is located in the intron between exon 1 and the non-coding exon 2, in which the coding sequence begins.

The frequency of CYP1A2 (-163) A> C varies greatly in populations: allele frequencies for allele C ranging from 0.3 to 0.39 in Asians, 0.4 to 0.51 in African and 0, 29 to 0.33 in Although polymorphism CYP1A2 * 1F is in a non-coding region of the gene, it can determine differential ties of regulatory proteins to the sequence surrounding that may affect the expression levels of CYP1A2. Alternatively, the polymorphism may be in linkage disequilibrium with other SNPs that affect the inducibility of CYP1A2. Even if smokers metabolize caffeine more quickly than non-smokers because of the well known effect of induction of CYP1A2, the degree of induction among smokers is lower for the carriers of allele C. So, smokers carrying a genotype correlated to slow metabolism of caffeine may still have an increased risk of myocardial infarction by increasing coffee consumption.