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The variations in the cytochrome P450 genes (CYP) lead to four different metabolizer phenotypes: ultrarapid, extensive, intermediate and poor.
A patient with a ultrarapid drug metabolism bears double or multiple copies of an allele with normal or increased functionality, whereas patients with intermediate or poor drug metabolism bear one or more alleles with reduced functionality (these alleles are typically consistent with inactivating mutations or large gene deletions). The term extensive metabolizer is used instead to describe those individuals with two standard copies of the normally functional allele. Extensive metabolizers are therefore carrying the wild-type allele, also called consensus allele, which corresponds to the allele *1 in the star allele nomenclature. The numbers *2, *3, *4 and so on represent alleles with altered functionality which may lead to profiles of increased or reduced drug metabolism.
By using one single star allele one can identify not just a single variant, but even a group of variants. Rules are as follows:
A) to distinguish an allele of proved pharmacogenomic relevance from a group of alleles where this allele is segregating together with other neutral alleles, numbers and letters are used.
Example: the symbol CYP2B6*4A identifies the pharmacogenomic relevant allele K262R in the CYP2B6 gene, whereas the symbol CYP2B6*4B identifies the combination of the K262R allele with one or more of the polymorphisms which can be easily detected in association with it: -2320T>C; -1778A>G; -1186C>G; -750T>C; 18053A>G. In both cases (CYP2B6*4A and CYP2B6*4B) the pharmacogenomic effect remains the one of K262R.
B) similarly, to identify group of functional alleles, the number of the most "powerful" allele is always used, followed by a letter.
Example: the symbol CYP2C19*2 identifies the splice mutation 681G>A, which reduces the protein functionality. Other variants which also show some functional effect can often segregate in association with this splice mutation. However, the effect of the associated variants is always less relevant than the effect exerted by the splice mutation 681G>A. So different groups of associated alleles can be represented as follows:
CYP2C19*2A: 99C>T; 681G>A; 990C>T; 991A>G
CYP2C192*B: 99C>T; 276G>C; 681G>A; 990C>T; 991A>G
CYP2C19*C: 99C>T; 481G>C; 681G>A; 990C>T; 991A>G
In all cases, the final pharmacogenomic effect which can be observed at the clinical level is always the one given by the splice mutation 681G>A.
Of note, the first alleles described in the CYP genes family did not follow these rules exactly, nevertheless their original nomenclature is still used for simplicity.
