Genetic variations and haplotypes of CYP2C19 in a Japanese population.
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Fukushima-Uesaka H, Saito Y, Maekawa K, Ozawa S, Hasegawa R, Kajio H, Kuzuya N, Yasuda K, Kawamoto M, Kamatani N, Suzuki K, Yanagawa T, Tohkin M, Sawada J
Genetic variations and haplotypes of CYP2C19 in a Japanese population.
Drug Metab Pharmacokinet. 2005 Aug;20(4):300-7.
- PubMed ID
- 16141610 [ View in PubMed]
- Abstract
Forty-eight single nucleotide variations, including 27 novel ones, were found in the 5'- regulatory region, all of the exons and their surrounding introns of CYP2C19 in 253 Japanese subjects (134 diabetic patients and 119 healthy volunteers). Identified novel variations were as follows: -2772G>A, 2767_-2760delGGTGAACA, -2720T>C, -2547delG, -2545G>T, -2545_-2544 delGC, and -2040C>T in the enhancer region; -778C>T, -777G>A, -529G>C, -189C>A, and -185A>G in the promoter region; 151A>G (S51G), 481G>C (A161P), 986G>A (R329H), 1078G>A (D360N), and 1119C>T (D373D) in the exons, and IVS1+128T>A, IVS3+163G>A, IVS4+271A>G, IVS5-49A>G, IVS6-210C>T, IVS6-196T>A, IVS6-32T>A, IVS7+84G>A, IVS7-174C>T, and IVS8+64C>T in the introns. Since we found no significant differences in the variation frequencies between healthy volunteers and diabetic patients, the data for all subjects were treated as one group in further analysis. The allele frequencies were 0.265 for IVS6-196T>A, 0.045 for -2772G>A and -2720T>C, 0.024 for -2040C>T, 0.014 for IVS7-174C>T, 0.010 for -529G>C, 0.006 for IVS1+128T>A and 481G>C (A161P), 0.004 for -2767_-2760delGGTGAACA and IVS6-210C>T, and 0.002 for the other 17 variations. In addition, the two known nonsynonymous single nucleotide polymorphisms, 681G>A (splicing defect, (*)2 allele) and 636G>A (W212X; (*)3 allele) were detected at 0.267 and 0.128 frequencies, respectively. No variation was detected in the known binding sites for constitutive androstane receptor and glucocorticoid receptor. Linkage disequilibrium analysis showed several close linkages of variations throughout the gene. By using the variations, thirty-one haplotypes of CYP2C19 and their frequencies were estimated. Our results would provide fundamental and useful information for genotyping CYP2C19 in the Japanese and probably other Asian populations.
DrugBank Data that Cites this Article
- Polypeptides
Name UniProt ID Cytochrome P450 2C19 P33261 Details - Pharmaco-genomics
Drug Interacting Gene/Enzyme Allele name Genotypes Defining change(s) Type(s) Description Details Amitriptyline Cytochrome P450 2C19
Gene symbol: CYP2C19
UniProt: P33261CYP2C19*2A Not Available - 681G>A (rs4244285)
ADR Inferred Those with the AA or AG genotype are poor metabolizers of amitriptyline Details Amitriptyline Cytochrome P450 2C19
Gene symbol: CYP2C19
UniProt: P33261CYP2C19*3 Not Available - 636G>A (rs4986893)
ADR Inferred Those with the AA or AG genotype are poor metabolizers of amitriptyline Details Omeprazole Cytochrome P450 2C19
Gene symbol: CYP2C19
UniProt: P33261CYP2C19*2A Not Available - 681G>A (rs4244285)
Effect Inferred Poor metabolizer, lower dose requirement, improved drug efficacy Details Clobazam Cytochrome P450 2C19
Gene symbol: CYP2C19
UniProt: P33261CYP2C19*2A Not Available - 681G>A (rs4244285)
ADR Inferred Clobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2. Details Clobazam Cytochrome P450 2C19
Gene symbol: CYP2C19
UniProt: P33261CYP2C19*3 Not Available - 636G>A (rs4986893)
ADR Inferred Clobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2. Details Lansoprazole Cytochrome P450 2C19
Gene symbol: CYP2C19
UniProt: P33261CYP2C19*2A Not Available - 681G>A (rs4244285)
Effect Inferred Poor metabolizer, lower dose requirement, improved drug efficacy Details Mephenytoin Cytochrome P450 2C19
Gene symbol: CYP2C19
UniProt: P33261CYP2C19*2A Not Available - 681G>A (rs4244285)
Effect Inferred Poor metabolizer, lower dose requirement Details Esomeprazole Cytochrome P450 2C19
Gene symbol: CYP2C19
UniProt: P33261CYP2C19*2A Not Available - 681G>A (rs4244285)
Effect Inferred Poor metabolizer, lower dose requirement, improved drug efficacy Details Clopidogrel Cytochrome P450 2C19
Gene symbol: CYP2C19
UniProt: P33261CYP2C19*2A Not Available - 681G>A (rs4244285)
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for drug-drug interactions Details Clopidogrel Cytochrome P450 2C19
Gene symbol: CYP2C19
UniProt: P33261CYP2C19*3 Not Available - 636G>A (rs4986893)
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for drug-drug interactions Details Proguanil Cytochrome P450 2C19
Gene symbol: CYP2C19
UniProt: P33261CYP2C19*2A Not Available - 681G>A (rs4244285)
Effect Inferred Poor metabolizer, lower dose requirement Details Gliclazide Cytochrome P450 2C19
Gene symbol: CYP2C19
UniProt: P33261CYP2C19*2A Not Available - 681G>A (rs4244285)
Effect Inferred Poor drug metabolizer. Details