The PharmVar CYP3A5 expert panel has undertaken an extensive review of CYP3A5 allelic variation which led to the retirement of three star alleles, namely CYP3A5*2, *4 and *5. Based on new data, their defining variants were always found together with the CYP3A5*3-defining splice defect (c.219-237) meaning that their variants are part of CYP3A5*3 haplotypes and do not occur on their own as previously assumed. Specifically, c.1193C>A (formerly defining CYP3A5*2) is now part of the CYP3A5*3.010 suballele, c.599A>G (formerly defining CYP3A5*4) is now part of the CYP3A5*3.009 suballele, and c.432+2T>C is part of the CYP3A5*3.005 suballele which has first been described in 2003 as published as CYP3A5*3G.
This update makes genotype testing and analysis simpler moving forward. CYP3A5*2, *4 and *5 no longer need to be tested as they are tagged by the CYP3A5*3 variant and thereby accurately identified and reported as CYP3A5*3. Note that in the past, a patient who tested homozygous for c.219-237 (CYP3A5*3) and heterozygous for c.1193C>A (CYP3A5*2) may have been reported as having a CYP3A5*3/*3+*2 diplotype.
This update on CYP3A5 nomenclature is now shown on the PharmVar CYP3A5 page and is described in more detail in the PharmVar CYP3A5 GeneFocus review published in Clinical Pharmacology and Therapeutics.
PharmGKB, CPIC and PharmCAT have been updated accordingly to reflect this change.
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