title: Functionally defective or altered CYP3A4 and CYP3A5 single nucleotide polymorphisms and their detection with genotyping tests.
abstract: Among the four cytochrome P450 (CYP)3A genes, CYP3A4 and CYP3A5 are the most abundantly expressed in the human liver. Eighty single nucleotide polymorphisms (SNPs) of CYP3A4/5 have been reported to the Human P450 Allele Nomenclature Committee. CYP3A4 alleles with minimal function compared with wild type include the CYP3A4*6 and CYP3A4*17. Alleles with moderately decreased or altered activity include: CYP3A4*2, *8, *11, *12, *13, *16, and *18. CYP3A5 alleles with minimal function include the splice variants CYP3A5*3, *5, *6 and CYP3A5* 10, as well as the null allele CYP3A5*7. Alleles with moderately decreased catalytic activity include CYP3A5*8 and CYP3A5*9. This report reviews the current progress in the functional characterization of CYP3A4 and CYP3A5 SNPs and provides genotyping tests for possible defective variants. A combination of genotyping tests for defective CYP3A4/CYP3A5 haplotypes will be necessary to understand the variations in the metabolism and clinical toxicity of a wide variety of clinical drugs, since these two CYP proteins have overlapping substrate specificities.
authors: National Institutes of Health, National Institute of Environmental Health Science Center, NC 27709,USA. lee13@niehs.nih.gov
authors: Su-Jun
authors: SJ
authors: Lee
authors: Joyce A
authors: JA
authors: Goldstein
mesh_terms: D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D010597:Pharmacogenetics / Q000379:methods*; D020641:Polymorphism, Single Nucleotide
chemical_list: D003577:Cytochrome P-450 Enzyme System; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human