Functional Characterization of Novel Allelic Variants of CYP2C9 Recently Discovered in Southeast Asians
CYP2C9 was recently resequenced in 150 Asian subjects from Singapore. Several new coding variants were reported, and these variants are now named CYP2C9*14 (R125H), CYP2C9*15 (S162X), CYP2C9*16 (T299A), CYP2C9*17 (P382S), CYP2C9*18 (D397A), and CYP2C9*19 (Q454H). The CYP2C9*18 variant also contained...
Saved in:
| Published in | The Journal of pharmacology and experimental therapeutics Vol. 315; no. 3; pp. 1085 - 1090 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
01.12.2005
American Society for Pharmacology and Experimental Therapeutics |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0022-3565 1521-0103 |
| DOI | 10.1124/jpet.105.091181 |
Cover
| Abstract | CYP2C9 was recently resequenced in 150 Asian subjects from Singapore. Several new coding variants were reported, and these variants are now named CYP2C9*14 (R125H), CYP2C9*15 (S162X), CYP2C9*16 (T299A), CYP2C9*17 (P382S), CYP2C9*18 (D397A), and CYP2C9*19 (Q454H). The CYP2C9*18 variant also contained an I359L change previously associated with the CYP2C9*3 allele. In this study, we assessed the functional consequences of the new coding changes. cDNAs containing each of the new coding changes were constructed by site-directed mutagenesis and expressed in a bacterial cDNA expression system, the allelic proteins were partially purified, and their ability to hydroxylate a prototype CYP2C9 substrate was assayed. Expression of cDNAs in Escherichia coli containing either the D397A change or the S162X (premature stop codon) could not be detected either spectrally or at the apoprotein level. CYP2C9.14 and CYP2C9.16 exhibited 80 to 90% lower catalytic activity toward tolbutamide at two substrate concentrations compared with wild-type CYP2C9.1. Kinetic analysis confirmed that CYP2C9.14 and CYP2C9.16 have a higher Km and a >90% lower intrinsic clearance of tolbutamide compared with wild-type CYP2C9.1. Both CYP2C9.17 and CYP2C9.19 proteins exhibited modest 30 to 40% decreases in catalytic activity toward tolbutamide. Thus, CYP2C9*15 and CYP2C9*18 may represent null alleles, whereas CYP2C9*14 and CYP2C9*16 allelic variants produce proteins that are clearly catalytically defective in vitro, indicating the existence of new defective putative alleles of CYP2C9 in Asians. |
|---|---|
| AbstractList | CYP2C9 was recently resequenced in 150 Asian subjects from Singapore. Several new coding variants were reported, and these variants are now named CYP2C9*14 (R125H), CYP2C9*15 (S162X), CYP2C9*16 (T299A), CYP2C9*17 (P382S), CYP2C9*18 (D397A), and CYP2C9*19 (Q454H). The CYP2C9*18 variant also contained an I359L change previously associated with the CYP2C9*3 allele. In this study, we assessed the functional consequences of the new coding changes. cDNAs containing each of the new coding changes were constructed by site-directed mutagenesis and expressed in a bacterial cDNA expression system, the allelic proteins were partially purified, and their ability to hydroxylate a prototype CYP2C9 substrate was assayed. Expression of cDNAs in Escherichia coli containing either the D397A change or the S162X (premature stop codon) could not be detected either spectrally or at the apoprotein level. CYP2C9.14 and CYP2C9.16 exhibited 80 to 90% lower catalytic activity toward tolbutamide at two substrate concentrations compared with wild-type CYP2C9.1. Kinetic analysis confirmed that CYP2C9.14 and CYP2C9.16 have a higher Km and a >90% lower intrinsic clearance of tolbutamide compared with wild-type CYP2C9.1. Both CYP2C9.17 and CYP2C9.19 proteins exhibited modest 30 to 40% decreases in catalytic activity toward tolbutamide. Thus, CYP2C9*15 and CYP2C9*18 may represent null alleles, whereas CYP2C9*14 and CYP2C9*16 allelic variants produce proteins that are clearly catalytically defective in vitro, indicating the existence of new defective putative alleles of CYP2C9 in Asians.CYP2C9 was recently resequenced in 150 Asian subjects from Singapore. Several new coding variants were reported, and these variants are now named CYP2C9*14 (R125H), CYP2C9*15 (S162X), CYP2C9*16 (T299A), CYP2C9*17 (P382S), CYP2C9*18 (D397A), and CYP2C9*19 (Q454H). The CYP2C9*18 variant also contained an I359L change previously associated with the CYP2C9*3 allele. In this study, we assessed the functional consequences of the new coding changes. cDNAs containing each of the new coding changes were constructed by site-directed mutagenesis and expressed in a bacterial cDNA expression system, the allelic proteins were partially purified, and their ability to hydroxylate a prototype CYP2C9 substrate was assayed. Expression of cDNAs in Escherichia coli containing either the D397A change or the S162X (premature stop codon) could not be detected either spectrally or at the apoprotein level. CYP2C9.14 and CYP2C9.16 exhibited 80 to 90% lower catalytic activity toward tolbutamide at two substrate concentrations compared with wild-type CYP2C9.1. Kinetic analysis confirmed that CYP2C9.14 and CYP2C9.16 have a higher Km and a >90% lower intrinsic clearance of tolbutamide compared with wild-type CYP2C9.1. Both CYP2C9.17 and CYP2C9.19 proteins exhibited modest 30 to 40% decreases in catalytic activity toward tolbutamide. Thus, CYP2C9*15 and CYP2C9*18 may represent null alleles, whereas CYP2C9*14 and CYP2C9*16 allelic variants produce proteins that are clearly catalytically defective in vitro, indicating the existence of new defective putative alleles of CYP2C9 in Asians. CYP2C9 was recently resequenced in 150 Asian subjects from Singapore. Several new coding variants were reported, and these variants are now named CYP2C9*14 (R125H), CYP2C9*15 (S162X), CYP2C9*16 (T299A), CYP2C9*17 (P382S), CYP2C9*18 (D397A), and CYP2C9*19 (Q454H). The CYP2C9*18 variant also contained an I359L change previously associated with the CYP2C9*3 allele. In this study, we assessed the functional consequences of the new coding changes. cDNAs containing each of the new coding changes were constructed by site-directed mutagenesis and expressed in a bacterial cDNA expression system, the allelic proteins were partially purified, and their ability to hydroxylate a prototype CYP2C9 substrate was assayed. Expression of cDNAs in Escherichia coli containing either the D397A change or the S162X (premature stop codon) could not be detected either spectrally or at the apoprotein level. CYP2C9.14 and CYP2C9.16 exhibited 80 to 90% lower catalytic activity toward tolbutamide at two substrate concentrations compared with wild-type CYP2C9.1. Kinetic analysis confirmed that CYP2C9.14 and CYP2C9.16 have a higher Km and a >90% lower intrinsic clearance of tolbutamide compared with wild-type CYP2C9.1. Both CYP2C9.17 and CYP2C9.19 proteins exhibited modest 30 to 40% decreases in catalytic activity toward tolbutamide. Thus, CYP2C9*15 and CYP2C9*18 may represent null alleles, whereas CYP2C9*14 and CYP2C9*16 allelic variants produce proteins that are clearly catalytically defective in vitro, indicating the existence of new defective putative alleles of CYP2C9 in Asians. CYP2C9 was recently resequenced in 150 Asian subjects from Singapore. Several new coding variants were reported, and these variants are now named CYP2C9*14 (R125H), CYP2C9*15 (S162X), CYP2C9*16 (T299A), CYP2C9*17 (P382S), CYP2C9*18 (D397A), and CYP2C9*19 (Q454H). The CYP2C9*18 variant also contained an I359L change previously associated with the CYP2C9*3 allele. In this study, we assessed the functional consequences of the new coding changes. cDNAs containing each of the new coding changes were constructed by site-directed mutagenesis and expressed in a bacterial cDNA expression system, the allelic proteins were partially purified, and their ability to hydroxylate a prototype CYP2C9 substrate was assayed. Expression of cDNAs in Escherichia coli containing either the D397A change or the S162X (premature stop codon) could not be detected either spectrally or at the apoprotein level. CYP2C9.14 and CYP2C9.16 exhibited 80 to 90% lower catalytic activity toward tolbutamide at two substrate concentrations compared with wild-type CYP2C9.1. Kinetic analysis confirmed that CYP2C9.14 and CYP2C9.16 have a higher K m and a >90% lower intrinsic clearance of tolbutamide compared with wild-type CYP2C9.1. Both CYP2C9.17 and CYP2C9.19 proteins exhibited modest 30 to 40% decreases in catalytic activity toward tolbutamide. Thus, CYP2C9*15 and CYP2C9*18 may represent null alleles, whereas CYP2C9*14 and CYP2C9*16 allelic variants produce proteins that are clearly catalytically defective in vitro, indicating the existence of new defective putative alleles of CYP2C9 in Asians. |
| Author | Lee, Soo-Chin Coulter, Sherry J. Goldstein, Joyce A. DeLozier, Tracy C. Goh, Boon Cher |
| Author_xml | – sequence: 1 givenname: Tracy C. surname: DeLozier fullname: DeLozier, Tracy C. – sequence: 2 givenname: Soo-Chin surname: Lee fullname: Lee, Soo-Chin – sequence: 3 givenname: Sherry J. surname: Coulter fullname: Coulter, Sherry J. – sequence: 4 givenname: Boon Cher surname: Goh fullname: Goh, Boon Cher – sequence: 5 givenname: Joyce A. surname: Goldstein fullname: Goldstein, Joyce A. email: goldste1@niehs.nih.gov |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/16099926$$D View this record in MEDLINE/PubMed |
| BookMark | eNp9kUtv1DAURi1URKeFNTvkFawy9SNxnOUo0IJUAeIlsbIc52bGlSee2k7R9NfjkCIkJFhZ1_cc2_fzGToZ_QgIPadkTSkrL24OkNaUVGvSUCrpI7SiFaMFoYSfoBUhjBW8EtUpOovxhhBaloI_QadUkKZpmFih7eU0mmT9qB1udzpokyDYez1vYT_g9_4OHN44B84a_E0Hq8cU5077_SNrG_wJDIzJHfFrG02GA_TYjvizn9IOdEx4E7MSn6LHg3YRnj2s5-jr5Zsv7dvi-sPVu3ZzXZhSlqmouQBW97wRgkJT8ppxXg1yKOtSa65FXfJe5ulYJ7rOSMm0FLLuDZvH76Th5-jlcu4h-NsJYlL7_C5wTo_gp6iEzHpViwy-eACnbg-9OgS71-GofkeTgYsFMMHHGGD4gxA1h6_m8HNRqSX8bFR_GcamX0mmoK37j_dq8XZ2u_thA6hD_om9Nt757VFxWimeeVllsllIyBHeWQgqGgujgT5bJqne23_e8hMViqj_ |
| CitedBy_id | crossref_primary_10_1038_clpt_2008_10 crossref_primary_10_1080_08927022_2018_1513646 crossref_primary_10_1002_chir_22289 crossref_primary_10_2217_pgs_2020_0051 crossref_primary_10_1038_clpt_2008_213 crossref_primary_10_1016_j_drudis_2016_09_015 crossref_primary_10_1016_j_arr_2010_06_001 crossref_primary_10_1016_j_gene_2020_144659 crossref_primary_10_1016_j_oooo_2020_06_021 crossref_primary_10_1016_j_jinorgbio_2024_112622 crossref_primary_10_1124_dmd_118_084269 crossref_primary_10_3390_genes9100514 crossref_primary_10_1053_j_gastro_2009_02_045 crossref_primary_10_1186_s40203_016_0016_7 crossref_primary_10_1111_bcpt_12159 crossref_primary_10_1038_sj_tpj_6500410 crossref_primary_10_1097_FPC_0b013e328344c340 crossref_primary_10_1111_j_1365_2125_2006_02679_x crossref_primary_10_1002_bdd_2153 crossref_primary_10_1038_tpj_2013_2 crossref_primary_10_1291_hypres_31_1549 crossref_primary_10_1007_s11274_006_9158_9 crossref_primary_10_1097_CAD_0b013e3280109411 crossref_primary_10_1097_01_fpc_0000215069_14095_c6 crossref_primary_10_2217_pgs_14_47 crossref_primary_10_1007_s10928_009_9138_4 crossref_primary_10_1016_j_fct_2023_113926 crossref_primary_10_3390_jpm8010001 crossref_primary_10_1038_aps_2013_123 crossref_primary_10_2133_dmpk_DMPK_11_RV_090 crossref_primary_10_1038_tpj_2013_22 crossref_primary_10_1016_j_thromres_2006_10_021 crossref_primary_10_1517_17425255_2014_894020 crossref_primary_10_1016_j_jmoldx_2019_04_003 crossref_primary_10_1097_FPC_0b013e32831a9ae3 crossref_primary_10_1016_j_cbi_2016_04_040 crossref_primary_10_4062_biomolther_2019_112 crossref_primary_10_1517_17425250902970998 crossref_primary_10_1177_0091270008319329 crossref_primary_10_1515_dmdi_2020_0153 crossref_primary_10_1007_s13318_014_0245_2 crossref_primary_10_1016_j_pharep_2013_09_006 crossref_primary_10_3109_03639045_2014_950274 crossref_primary_10_1002_mgg3_283 crossref_primary_10_1016_j_blre_2007_11_004 crossref_primary_10_1016_j_cbi_2020_109168 crossref_primary_10_1016_j_gene_2013_03_128 crossref_primary_10_1515_dmpt_2020_0153 crossref_primary_10_1159_000381189 crossref_primary_10_3109_00498254_2013_820007 crossref_primary_10_1124_dmd_114_061200 crossref_primary_10_3389_fphar_2022_1007268 crossref_primary_10_1080_17425255_2024_2409255 crossref_primary_10_1021_acs_biochem_7b00795 crossref_primary_10_2147_DDDT_S268796 crossref_primary_10_1002_prp2_718 crossref_primary_10_1016_j_cbi_2022_109799 crossref_primary_10_1016_j_cca_2007_02_033 crossref_primary_10_1016_j_jmb_2013_07_010 crossref_primary_10_1007_s12272_011_1103_2 crossref_primary_10_1007_s00228_009_0707_7 crossref_primary_10_1124_dmd_114_060244 |
| Cites_doi | 10.1097/01.fpc.0000114759.08559.51 10.1016/j.clpt.2004.05.005 10.1517/14622416.5.7.895 10.1097/00008571-200112000-00008 10.1016/j.tibs.2004.11.004 10.1097/00008571-199608000-00007 10.1046/j.1365-2125.1998.00721.x 10.1074/jbc.271.21.12496 10.1006/abbi.1995.0013 10.1081/ERC-120016820 10.1038/nature02214 10.1016/S0169-409X(02)00076-5 10.1097/00007691-200006000-00001 10.1124/mol.60.2.382 10.1002/prot.20354 10.1097/01.fpc.0000114749.08559.e4 10.1097/00008571-200204000-00010 10.1038/nature01862 10.1124/jpet.103.058818 10.1182/blood-2003-07-2521 10.1074/jbc.273.27.17036 10.1067/mcp.2001.117444 10.1016/S0021-9258(20)82245-5 10.1093/hmg/ddi180 10.1016/S0009-8981(03)00319-X 10.1111/j.1472-8206.2004.00307.x 10.1021/bi00173a017 10.1146/annurev.pharmtox.41.1.815 10.1182/blood-2004-06-2111 10.1067/mcp.2001.117367 10.1097/00008571-200412000-00004 10.1097/00008571-199706000-00005 |
| ContentType | Journal Article |
| Copyright | 2005 American Society for Pharmacology and Experimental Therapeutics |
| Copyright_xml | – notice: 2005 American Society for Pharmacology and Experimental Therapeutics |
| DBID | AAYXX CITATION CGR CUY CVF ECM EIF NPM 7X8 |
| DOI | 10.1124/jpet.105.091181 |
| DatabaseName | CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed MEDLINE - Academic |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) MEDLINE - Academic |
| DatabaseTitleList | MEDLINE - Academic MEDLINE |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Pharmacy, Therapeutics, & Pharmacology |
| EISSN | 1521-0103 |
| EndPage | 1090 |
| ExternalDocumentID | 16099926 10_1124_jpet_105_091181 315_3_1085 S002235652432350X |
| Genre | Journal Article Comparative Study |
| GeographicLocations | China Singapore India |
| GeographicLocations_xml | – name: Singapore – name: China – name: India |
| GroupedDBID | --- -~X .55 .GJ 0R~ 18M 2WC 3O- 4.4 53G 5GY 5RE 5VS 8WZ A6W AAJMC AALRI AAXUO AAYOK ABCQX ABIVO ABJNI ABOCM ABSQV ACGFO ACGFS ACNCT ADBBV ADCOW ADIYS AENEX AERNN AFFNX AFHIN AFOSN AGFXO AI. ALMA_UNASSIGNED_HOLDINGS BAWUL BTFSW CS3 DIK DU5 E3Z EBS EJD F5P F9R FDB GX1 H13 HZ~ INIJC KQ8 L7B LSO M41 MJL MVM O9- OHT OK1 P2P PKN R.V R0Z RHF RHI ROL RPT TR2 UQL VH1 W2D W8F WH7 WOQ X7M YBU YHG YQT ZGI ZXP - 08R 0R 55 8RP AALRV ABFLS ABSGY ABZEH ACDCL ADACO ADBIT ADKFC AETEA AIKQT DL FH7 GJ HZ O0- X AAYXX ACVFH ADCNI AEUPX AFPUW AIGII AKBMS AKYEP CITATION CGR CUY CVF ECM EIF NPM 7X8 |
| ID | FETCH-LOGICAL-c484t-736e27d39661e94372335f8f474aa3a6743d80102b6bbc882a8687dc29118b8c3 |
| ISSN | 0022-3565 |
| IngestDate | Fri Sep 05 02:47:17 EDT 2025 Sat Mar 08 01:25:16 EST 2025 Tue Jul 01 05:41:09 EDT 2025 Thu Apr 24 22:55:10 EDT 2025 Tue Jan 05 21:16:50 EST 2021 Sat Feb 22 15:44:56 EST 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 3 |
| Language | English |
| LinkModel | OpenURL |
| MergedId | FETCHMERGED-LOGICAL-c484t-736e27d39661e94372335f8f474aa3a6743d80102b6bbc882a8687dc29118b8c3 |
| Notes | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 |
| OpenAccessLink | http://scholarbank.nus.edu.sg/handle/10635/27207 |
| PMID | 16099926 |
| PQID | 68801576 |
| PQPubID | 23479 |
| PageCount | 6 |
| ParticipantIDs | proquest_miscellaneous_68801576 pubmed_primary_16099926 crossref_primary_10_1124_jpet_105_091181 crossref_citationtrail_10_1124_jpet_105_091181 highwire_pharmacology_315_3_1085 elsevier_sciencedirect_doi_10_1124_jpet_105_091181 |
| ProviderPackageCode | RHF RHI CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | December 2005 20051201 2005-12-00 2005-Dec |
| PublicationDateYYYYMMDD | 2005-12-01 |
| PublicationDate_xml | – month: 12 year: 2005 text: December 2005 |
| PublicationDecade | 2000 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | The Journal of pharmacology and experimental therapeutics |
| PublicationTitleAlternate | J Pharmacol Exp Ther |
| PublicationYear | 2005 |
| Publisher | Elsevier Inc American Society for Pharmacology and Experimental Therapeutics |
| Publisher_xml | – name: Elsevier Inc – name: American Society for Pharmacology and Experimental Therapeutics |
| References | mephenytoin 4′-hydroxylase in humans. 17036–17049. Loebstein R, Yonath H, Peleg D, Almog S, Rotenberg M, Lubetsky A, Roitelman J, Harats D, Halkin H, and Ezra D (2001) Interindividual variability in sensitivity to warfarin: nature or nurture? Solus JF, Arietta BJ, Harris JR, Sexton DP, Steward JQ, McMunn C, Ihrie P, Mehall JM, Edwards TL, and Dawson EP (2004) Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population. Richardson TH, Jung F, Griffin KJ, Wester M, Raucy JL, Kemper B, Bornheim LM, Hassett C, Omiecinski CJ, and Johnson EF (1995) A universal approach to the expression of human and rabbit cytochrome P450s of the 2C subfamily in 341–349. D’Andrea G, D’Ambrosio RL, Di Perna P, Chetta M, Santacroce R, Brancaccio V, Grandone E, and Margaglione M (2005) A polymorphism in the VKORC1 gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin. 527–537. Kidd RS, Curry TB, Gallagher S, Edeki T, Blaisdell J, and Goldstein JA (2001) Identification of a null allele of CYP2C9 in an African-American exhibiting toxicity to phenytoin. 596–609. 1257–1270. Zainuddin Z, Teh LK, Suhaimi AW, Salleh MZ, and Ismail R (2003) A simple method for the detection of CYP2C9 polymorphisms: nested allele-specific multiplex polymerase chain reaction. 12496–12501. 2379–2385. 87–96. 1745–1751. 1510–1516. Xie HG, Kim RB, Wood AJ, and Stein CM (2001) Molecular basis of ethnic differences in drug disposition and response. 815–850. Shintani M, Ieiri I, Inoue K, Mamiya K, Ninomiya H, Tashiro N, Higuchi S, and Otsubo K (2001) Genetic polymorphisms and functional characterization of the 5′-flanking region of the human CYP2C9 gene: in vitro and in vivo studies. Lee CR, Goldstein JA, and Pieper JA (2002) Cytochrome P450 2C9 polymorphisms: a comprehensive review of the in-vitro and human data. D’Ambrosio RL, D’Andrea G, Cappucci F, Chetta M, Di Perna P, Brancaccio V, Grandone E, and Margaglione M (2004) Polymorphisms in factor II and factor VII genes modulate oral anticoagulation with warfarin. 101–105. 803–808. Yuan HY, Chen JJ, Lee MT, Wung JC, Chen YF, Charng MJ, Lu MJ, Hung CR, Wei CY, Chen CH, et al. (2005) A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity. . Jose R, Chandrasekaran A, Sam SS, Gerard N, Chanolean S, Abraham BK, Satyanarayanamoorthy K, Peter A, and Rajagopal K (2005) CYP2C9 and CYP2C19 genetic polymorphisms: frequencies in the south Indian population. Ieiri I, Tainaka H, Morita T, Hadama A, Mamiya K, Hayashibara M, Ninomiya H, Ohmori S, Kitada M, Tashiro N, et al. (2000) Catalytic activity of three variants (Ile, Leu and Thr) at amino acid residue 359 in human CYP2C9 gene and simultaneous detection using single-strand conformation polymorphism analysis. Zhao F, Loke C, Rankin SC, Guo JY, Lee HS, Wu TS, Tan T, Liu TC, Lu WL, Lim YT, et al. (2004) Novel CYP2C9 genetic variants in Asian subjects and their influence on maintenance warfarin dose. Ibeanu GC, Ghanayem BI, Linko P, Li L, Pedersen LG, and Goldstein JA (1996) Identification of residues 99, 220 and 221 of human cytochrome P450 2C19 as key determinants of omeprazole hydroxylase activity. Scott EE and Halpert JR (2005) Structures of cytochrome P450 3A4. Si D, Guo Y, Zhang Y, Yang L, Zhou H, and Zhong D (2004) Identification of a novel variant CYP2C9 allele in Chinese. Sullivan-Klose TH, Ghanayem BI, Bell DA, Zhang ZY, Kaminsky LS, Shenfield GM, Miners JO, Birkett DJ, and Goldstein JA (1996) The role of the CYP2C9-Leu359 allelic variant in the tolbutamide polymorphism. 203–210. 537–541. 3055–3057. 495–501. 237–244. 464–468. Crespi CL and Miller VP (1997) The R144C change in the CYP2C9*2 allele alters interaction of the cytochrome P450 with NADPH:cytochrome P450 oxidoreductase. 5–7. 465–469. 645–649. Blaisdell J, Jorge-Nebert LF, Coulter S, Ferguson SS, Lee SJ, Chanas B, Xi T, Mohrenweiser H, Ghanayem B, and Goldstein JA (2004) Discovery of new potentially defective alleles of human CYP2C9. 175–182. Takahashi H, Ieiri I, Wilkinson GR, Mayo G, Kashima T, Kimura S, Otsubo K, and Echizen H (2004) 5′-Flanking region polymorphisms of CYP2C9 and their relationship to S-warfarin metabolism in white and Japanese patients. 1743–1752. Chen Y, Ferguson SS, Negishi M, and Goldstein JA (2004) Induction of human CYP2C9 by rifampicin, hyperforin and phenobarbital is mediated by the pregnane X receptor. Rost S, Fregin A, Ivaskevicius V, Conzelmann E, Hortnagel K, Pelz HJ, Lappegard K, Seifried E, Scharrer I, Tuddenham EG, et al. (2004) Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. Xie HG, Prasad HC, Kim RB, and Stein CM (2002) CYP2C9 allelic variants: ethnic distribution and functional significance. 382–387. Dickmann LJ, Rettie AE, Kneller MB, Kim RB, Wood AJ, Stein CM, Wilkinson GR, and Schwarz UI (2001) Identification and functional characterization of a new CYP2C9 variant (CYP2C9*5) expressed among African Americans. 813–822. 97–102. Goldstein JA, Faletto MB, Romkes-Sparks M, Sullivan T, Kitareewan S, Raucy JL, Lasker JM, and Ghanayem BI (1994) Evidence that CYP2C19 is the major Mestres J (2004) Structure conservation in cytochromes P450. 159–164. Omura T and Sato R (1964) The carbon monoxide-binding pigment of liver microsomes: II. Solubilization, purification and properties. Johnson EF, Wester MR, and Stout CD (2002) The structure of microsomal cytochrome P450 2C5: a steroid and drug metabolizing enzyme. Bridges A, Gruenke L, Chang YT, Vakser IA, Loew G, and Waskell L (1998) Identification of the binding site on cytochrome P450 2B4 for cytochrome b5 and cytochrome P450 reductase. 251–263. King BP, Khan TI, Aithal GP, Kamali F, and Daly AK (2004) Upstream and coding region CYP2C9 polymorphisms: correlation with warfarin dose and metabolism. 525–538. Miners JO and Birkett DJ (1998) Cytochrome P4502C9: an enzyme of major importance in human drug metabolism. 435–441. 895–931. Williams PA, Cosme J, Ward A, Angove HC, Matak Vinkovic D, and Jhoti H (2003) Crystal structure of human cytochrome P450 2C9 with bound warfarin. 210–219. 10.1124/jpet.105.091181_bib29 10.1124/jpet.105.091181_bib26 10.1124/jpet.105.091181_bib25 10.1124/jpet.105.091181_bib28 10.1124/jpet.105.091181_bib27 10.1124/jpet.105.091181_bib22 10.1124/jpet.105.091181_bib21 10.1124/jpet.105.091181_bib24 10.1124/jpet.105.091181_bib23 10.1124/jpet.105.091181_bib9 10.1124/jpet.105.091181_bib20 10.1124/jpet.105.091181_bib2 10.1124/jpet.105.091181_bib1 10.1124/jpet.105.091181_bib4 10.1124/jpet.105.091181_bib3 10.1124/jpet.105.091181_bib6 10.1124/jpet.105.091181_bib5 10.1124/jpet.105.091181_bib8 10.1124/jpet.105.091181_bib7 10.1124/jpet.105.091181_bib19 10.1124/jpet.105.091181_bib18 10.1124/jpet.105.091181_bib15 10.1124/jpet.105.091181_bib14 10.1124/jpet.105.091181_bib17 10.1124/jpet.105.091181_bib16 10.1124/jpet.105.091181_bib11 10.1124/jpet.105.091181_bib33 10.1124/jpet.105.091181_bib10 10.1124/jpet.105.091181_bib32 10.1124/jpet.105.091181_bib13 10.1124/jpet.105.091181_bib12 10.1124/jpet.105.091181_bib31 10.1124/jpet.105.091181_bib30 |
| References_xml | – reference: 87–96. – reference: 17036–17049. – reference: Kidd RS, Curry TB, Gallagher S, Edeki T, Blaisdell J, and Goldstein JA (2001) Identification of a null allele of CYP2C9 in an African-American exhibiting toxicity to phenytoin. – reference: Williams PA, Cosme J, Ward A, Angove HC, Matak Vinkovic D, and Jhoti H (2003) Crystal structure of human cytochrome P450 2C9 with bound warfarin. – reference: 527–537. – reference: 97–102. – reference: Miners JO and Birkett DJ (1998) Cytochrome P4502C9: an enzyme of major importance in human drug metabolism. – reference: 2379–2385. – reference: 5–7. – reference: Bridges A, Gruenke L, Chang YT, Vakser IA, Loew G, and Waskell L (1998) Identification of the binding site on cytochrome P450 2B4 for cytochrome b5 and cytochrome P450 reductase. – reference: Crespi CL and Miller VP (1997) The R144C change in the CYP2C9*2 allele alters interaction of the cytochrome P450 with NADPH:cytochrome P450 oxidoreductase. – reference: Omura T and Sato R (1964) The carbon monoxide-binding pigment of liver microsomes: II. Solubilization, purification and properties. – reference: Johnson EF, Wester MR, and Stout CD (2002) The structure of microsomal cytochrome P450 2C5: a steroid and drug metabolizing enzyme. – reference: Xie HG, Prasad HC, Kim RB, and Stein CM (2002) CYP2C9 allelic variants: ethnic distribution and functional significance. – reference: 101–105. – reference: Zhao F, Loke C, Rankin SC, Guo JY, Lee HS, Wu TS, Tan T, Liu TC, Lu WL, Lim YT, et al. (2004) Novel CYP2C9 genetic variants in Asian subjects and their influence on maintenance warfarin dose. – reference: 803–808. – reference: D’Andrea G, D’Ambrosio RL, Di Perna P, Chetta M, Santacroce R, Brancaccio V, Grandone E, and Margaglione M (2005) A polymorphism in the VKORC1 gene is associated with an interindividual variability in the dose-anticoagulant effect of warfarin. – reference: 175–182. – reference: Blaisdell J, Jorge-Nebert LF, Coulter S, Ferguson SS, Lee SJ, Chanas B, Xi T, Mohrenweiser H, Ghanayem B, and Goldstein JA (2004) Discovery of new potentially defective alleles of human CYP2C9. – reference: 495–501. – reference: 813–822. – reference: 251–263. – reference: 1745–1751. – reference: Ieiri I, Tainaka H, Morita T, Hadama A, Mamiya K, Hayashibara M, Ninomiya H, Ohmori S, Kitada M, Tashiro N, et al. (2000) Catalytic activity of three variants (Ile, Leu and Thr) at amino acid residue 359 in human CYP2C9 gene and simultaneous detection using single-strand conformation polymorphism analysis. – reference: Xie HG, Kim RB, Wood AJ, and Stein CM (2001) Molecular basis of ethnic differences in drug disposition and response. – reference: 815–850. – reference: D’Ambrosio RL, D’Andrea G, Cappucci F, Chetta M, Di Perna P, Brancaccio V, Grandone E, and Margaglione M (2004) Polymorphisms in factor II and factor VII genes modulate oral anticoagulation with warfarin. – reference: 465–469. – reference: 1257–1270. – reference: . – reference: Ibeanu GC, Ghanayem BI, Linko P, Li L, Pedersen LG, and Goldstein JA (1996) Identification of residues 99, 220 and 221 of human cytochrome P450 2C19 as key determinants of omeprazole hydroxylase activity. – reference: 1510–1516. – reference: 1743–1752. – reference: 159–164. – reference: 596–609. – reference: Dickmann LJ, Rettie AE, Kneller MB, Kim RB, Wood AJ, Stein CM, Wilkinson GR, and Schwarz UI (2001) Identification and functional characterization of a new CYP2C9 variant (CYP2C9*5) expressed among African Americans. – reference: 537–541. – reference: Chen Y, Ferguson SS, Negishi M, and Goldstein JA (2004) Induction of human CYP2C9 by rifampicin, hyperforin and phenobarbital is mediated by the pregnane X receptor. – reference: King BP, Khan TI, Aithal GP, Kamali F, and Daly AK (2004) Upstream and coding region CYP2C9 polymorphisms: correlation with warfarin dose and metabolism. – reference: Rost S, Fregin A, Ivaskevicius V, Conzelmann E, Hortnagel K, Pelz HJ, Lappegard K, Seifried E, Scharrer I, Tuddenham EG, et al. (2004) Mutations in VKORC1 cause warfarin resistance and multiple coagulation factor deficiency type 2. – reference: Takahashi H, Ieiri I, Wilkinson GR, Mayo G, Kashima T, Kimura S, Otsubo K, and Echizen H (2004) 5′-Flanking region polymorphisms of CYP2C9 and their relationship to S-warfarin metabolism in white and Japanese patients. – reference: 237–244. – reference: 3055–3057. – reference: Solus JF, Arietta BJ, Harris JR, Sexton DP, Steward JQ, McMunn C, Ihrie P, Mehall JM, Edwards TL, and Dawson EP (2004) Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population. – reference: Goldstein JA, Faletto MB, Romkes-Sparks M, Sullivan T, Kitareewan S, Raucy JL, Lasker JM, and Ghanayem BI (1994) Evidence that CYP2C19 is the major ( – reference: Si D, Guo Y, Zhang Y, Yang L, Zhou H, and Zhong D (2004) Identification of a novel variant CYP2C9 allele in Chinese. – reference: 210–219. – reference: 203–210. – reference: Sullivan-Klose TH, Ghanayem BI, Bell DA, Zhang ZY, Kaminsky LS, Shenfield GM, Miners JO, Birkett DJ, and Goldstein JA (1996) The role of the CYP2C9-Leu359 allelic variant in the tolbutamide polymorphism. – reference: Richardson TH, Jung F, Griffin KJ, Wester M, Raucy JL, Kemper B, Bornheim LM, Hassett C, Omiecinski CJ, and Johnson EF (1995) A universal approach to the expression of human and rabbit cytochrome P450s of the 2C subfamily in – reference: Lee CR, Goldstein JA, and Pieper JA (2002) Cytochrome P450 2C9 polymorphisms: a comprehensive review of the in-vitro and human data. – reference: Loebstein R, Yonath H, Peleg D, Almog S, Rotenberg M, Lubetsky A, Roitelman J, Harats D, Halkin H, and Ezra D (2001) Interindividual variability in sensitivity to warfarin: nature or nurture? – reference: 382–387. – reference: Scott EE and Halpert JR (2005) Structures of cytochrome P450 3A4. – reference: Yuan HY, Chen JJ, Lee MT, Wung JC, Chen YF, Charng MJ, Lu MJ, Hung CR, Wei CY, Chen CH, et al. (2005) A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity. – reference: 12496–12501. – reference: Jose R, Chandrasekaran A, Sam SS, Gerard N, Chanolean S, Abraham BK, Satyanarayanamoorthy K, Peter A, and Rajagopal K (2005) CYP2C9 and CYP2C19 genetic polymorphisms: frequencies in the south Indian population. – reference: 645–649. – reference: Zainuddin Z, Teh LK, Suhaimi AW, Salleh MZ, and Ismail R (2003) A simple method for the detection of CYP2C9 polymorphisms: nested allele-specific multiplex polymerase chain reaction. – reference: )-mephenytoin 4′-hydroxylase in humans. – reference: 435–441. – reference: Mestres J (2004) Structure conservation in cytochromes P450. – reference: 895–931. – reference: Shintani M, Ieiri I, Inoue K, Mamiya K, Ninomiya H, Tashiro N, Higuchi S, and Otsubo K (2001) Genetic polymorphisms and functional characterization of the 5′-flanking region of the human CYP2C9 gene: in vitro and in vivo studies. – reference: 341–349. – reference: 464–468. – reference: 525–538. – ident: 10.1124/jpet.105.091181_bib1 doi: 10.1097/01.fpc.0000114759.08559.51 – ident: 10.1124/jpet.105.091181_bib33 doi: 10.1016/j.clpt.2004.05.005 – ident: 10.1124/jpet.105.091181_bib25 doi: 10.1517/14622416.5.7.895 – ident: 10.1124/jpet.105.091181_bib13 doi: 10.1097/00008571-200112000-00008 – ident: 10.1124/jpet.105.091181_bib22 doi: 10.1016/j.tibs.2004.11.004 – ident: 10.1124/jpet.105.091181_bib26 doi: 10.1097/00008571-199608000-00007 – ident: 10.1124/jpet.105.091181_bib18 doi: 10.1046/j.1365-2125.1998.00721.x – ident: 10.1124/jpet.105.091181_bib9 doi: 10.1074/jbc.271.21.12496 – ident: 10.1124/jpet.105.091181_bib20 doi: 10.1006/abbi.1995.0013 – ident: 10.1124/jpet.105.091181_bib11 doi: 10.1081/ERC-120016820 – ident: 10.1124/jpet.105.091181_bib5 – ident: 10.1124/jpet.105.091181_bib21 doi: 10.1038/nature02214 – ident: 10.1124/jpet.105.091181_bib30 doi: 10.1016/S0169-409X(02)00076-5 – ident: 10.1124/jpet.105.091181_bib10 doi: 10.1097/00007691-200006000-00001 – ident: 10.1124/jpet.105.091181_bib7 doi: 10.1124/mol.60.2.382 – ident: 10.1124/jpet.105.091181_bib17 doi: 10.1002/prot.20354 – ident: 10.1124/jpet.105.091181_bib24 doi: 10.1097/01.fpc.0000114749.08559.e4 – ident: 10.1124/jpet.105.091181_bib15 doi: 10.1097/00008571-200204000-00010 – ident: 10.1124/jpet.105.091181_bib28 doi: 10.1038/nature01862 – ident: 10.1124/jpet.105.091181_bib3 doi: 10.1124/jpet.103.058818 – ident: 10.1124/jpet.105.091181_bib27 doi: 10.1182/blood-2003-07-2521 – ident: 10.1124/jpet.105.091181_bib2 doi: 10.1074/jbc.273.27.17036 – ident: 10.1124/jpet.105.091181_bib16 doi: 10.1067/mcp.2001.117444 – ident: 10.1124/jpet.105.091181_bib19 doi: 10.1016/S0021-9258(20)82245-5 – ident: 10.1124/jpet.105.091181_bib31 doi: 10.1093/hmg/ddi180 – ident: 10.1124/jpet.105.091181_bib32 doi: 10.1016/S0009-8981(03)00319-X – ident: 10.1124/jpet.105.091181_bib12 doi: 10.1111/j.1472-8206.2004.00307.x – ident: 10.1124/jpet.105.091181_bib8 doi: 10.1021/bi00173a017 – ident: 10.1124/jpet.105.091181_bib29 doi: 10.1146/annurev.pharmtox.41.1.815 – ident: 10.1124/jpet.105.091181_bib6 doi: 10.1182/blood-2004-06-2111 – ident: 10.1124/jpet.105.091181_bib23 doi: 10.1067/mcp.2001.117367 – ident: 10.1124/jpet.105.091181_bib14 doi: 10.1097/00008571-200412000-00004 – ident: 10.1124/jpet.105.091181_bib4 doi: 10.1097/00008571-199706000-00005 |
| SSID | ssj0014463 |
| Score | 2.1195211 |
| Snippet | CYP2C9 was recently resequenced in 150 Asian subjects from Singapore. Several new coding variants were reported, and these variants are now named CYP2C9*14... CYP2C9 was recently resequenced in 150 Asian subjects from Singapore. Several new coding variants were reported, and these variants are now named CYP2C9*14... |
| SourceID | proquest pubmed crossref highwire elsevier |
| SourceType | Aggregation Database Index Database Enrichment Source Publisher |
| StartPage | 1085 |
| SubjectTerms | Alleles Aryl Hydrocarbon Hydroxylases - genetics Aryl Hydrocarbon Hydroxylases - isolation & purification Aryl Hydrocarbon Hydroxylases - metabolism Catalysis China - ethnology Cytochrome P-450 CYP2C9 DNA, Complementary Escherichia coli - genetics Genetic Variation Humans Hydroxylation India - ethnology Kinetics Mutagenesis, Site-Directed Polymorphism, Single Nucleotide Recombinant Proteins - isolation & purification Recombinant Proteins - metabolism Singapore Tolbutamide - metabolism Tolbutamide - pharmacokinetics Tolbutamide - pharmacology |
| Title | Functional Characterization of Novel Allelic Variants of CYP2C9 Recently Discovered in Southeast Asians |
| URI | https://dx.doi.org/10.1124/jpet.105.091181 http://jpet.aspetjournals.org/content/315/3/1085.abstract https://www.ncbi.nlm.nih.gov/pubmed/16099926 https://www.proquest.com/docview/68801576 |
| Volume | 315 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1bb9MwFLbKeOEFcacwwA9oQtpSWtu59BEitmlCUyU6VJ6s2HHGpCqZtnZS-3_4n5wTO05WrRLsJW3TOLfvi31OfM53CPmYGB0XeS6CTORhIAoeBkrFeSCyoci0hiHR1AGyp9HxmTiZhbNe708namm5UAO9vjOv5D6owjrAFbNk_wNZv1NYAd8BX1gCwrD8J4wPYVBy7_JSL7y89kbgaXVjAID53KCS9U_wipugl_TXhKVjtBlhzJmvUINTYyynQSWm_bqsHtb0AfCgyXXXgG1TyWoj9rJVvrZCTrcqBnSSu9r69eZ7tb5wRLnCYvPpYCMq6EdVBVjX28-PYO1rVyAMlSRX-ye-yVFVvxf6WsElp79dqHHzFiPciAjx6TW3oj9dqoEtJtF019ymfzpe8k7ni4kUnYEcQ07vHiSYwEECvBKscjwAi2lky8ZsKG_jRDbDwzPB4XM4e0AesjiuowGOZj6SCD1q7kXpYXOnIAWH-bxxkG3Gj9em3u7n1PbO9Al57DCmXyzrnpKeKZ-RvYnFe3VApx1sD-genXSY8Jyct9Skm9SkVUFralJHTdpQE_-x1KQNNWlLTXpRUk9Naqn5gpwdfpumx4Gr6RFokYhFEPPIsDjn4GWPzBgnjTkPi6QQscgynmFKTJ6gzqGKlNLg_mVJlMS5Znj_VKL5S7JTVqV5TajOVQZmw1hHIy1GQ6PGhQFrPEpgO8ZU3CeD5mZL7QTvse7KXNaOLxMS0YEfobTo9Mkn3-DSar1s35Q16ElnqloTVALJtjeiDc6y-3hKoLTkKNUb9smHBn8J_TxO3mWlqZbXEi4LLPc46pNXlhbtKUbo5bHozX3O6S151D6Ou2RncbU078DMXqj3Ncn_At3l1Qo |
| linkProvider | Geneva Foundation for Medical Education and Research |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Functional+Characterization+of+Novel+Allelic+Variants+of+CYP2C9+Recently+Discovered+in+Southeast+Asians&rft.jtitle=The+Journal+of+pharmacology+and+experimental+therapeutics&rft.au=DeLozier%2C+Tracy+C.&rft.au=Lee%2C+Soo-Chin&rft.au=Coulter%2C+Sherry+J.&rft.au=Goh%2C+Boon+Cher&rft.date=2005-12-01&rft.pub=Elsevier+Inc&rft.issn=0022-3565&rft.volume=315&rft.issue=3&rft.spage=1085&rft.epage=1090&rft_id=info:doi/10.1124%2Fjpet.105.091181&rft.externalDocID=S002235652432350X |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0022-3565&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0022-3565&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0022-3565&client=summon |