Digital PCR for determination of cytochrome P450 2D6 and sulfotransferase 1A1 gene copy number variations
CYP2D6 and SULT1A1 occasionally show copy number variations (CNVs), with a larger number generally indicating greater enzymic activity. However, those variations are difficult to calculate using standard methods. With digital PCR, a recently introduced method for CNV analysis, DNA molecules are subj...
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| Published in | Drug Discoveries & Therapeutics Vol. 11; no. 6; pp. 336 - 341 |
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| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
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Japan
International Research and Cooperation Association for Bio & Socio-Sciences Advancement
2017
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| Online Access | Get full text |
| ISSN | 1881-7831 1881-784X |
| DOI | 10.5582/ddt.2017.01057 |
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| Abstract | CYP2D6 and SULT1A1 occasionally show copy number variations (CNVs), with a larger number generally indicating greater enzymic activity. However, those variations are difficult to calculate using standard methods. With digital PCR, a recently introduced method for CNV analysis, DNA molecules are subjected to limited dilution and separated into nano-scale droplets prior to a PCR assay. Absolute quantitation of copy number can then be performed with high accuracy and sensitivity by determining the number of droplets showing an amplified signal for the target gene. This is the first report of analyses of CYP2D6 and SULT1A1 CNVs using a digital PCR method with blood sample from Japanese subject. Primers and probes were synthesized for the target and reference genes, and copy number calculation was performed using a QX200 Droplet Digital PCR System. Our results showed that the copy numbers in CYP2D6*5 hetero, non-CNV, and CYP2D6xN subjects were 1, 2, and 3 to 4, respectively. In addition, in non-CNV and multiplication subjects, the number of copies for SULT1A1 was 2 and 3 to 6, respectively. We found that the present digital PCR method was useful as well as accurate. In the future, a combined genotyping, allele distinction, and copy number calculation technique will be helpful for analysis of enzymic activity. |
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| AbstractList | CYP2D6 and SULT1A1 occasionally show copy number variations (CNVs), with a larger number generally indicating greater enzymic activity. However, those variations are difficult to calculate using standard methods. With digital PCR, a recently introduced method for CNV analysis, DNA molecules are subjected to limited dilution and separated into nano-scale droplets prior to a PCR assay. Absolute quantitation of copy number can then be performed with high accuracy and sensitivity by determining the number of droplets showing an amplified signal for the target gene. This is the first report of analyses of CYP2D6 and SULT1A1 CNVs using a digital PCR method with blood sample from Japanese subject. Primers and probes were synthesized for the target and reference genes, and copy number calculation was performed using a QX200 Droplet Digital PCR System. Our results showed that the copy numbers in CYP2D6*5 hetero, non-CNV, and CYP2D6xN subjects were 1, 2, and 3 to 4, respectively. In addition, in non-CNV and multiplication subjects, the number of copies for SULT1A1 was 2 and 3 to 6, respectively. We found that the present digital PCR method was useful as well as accurate. In the future, a combined genotyping, allele distinction, and copy number calculation technique will be helpful for analysis of enzymic activity. CYP2D6 and SULT1A1 occasionally show copy number variations (CNVs), with a larger number generally indicating greater enzymic activity. However, those variations are difficult to calculate using standard methods. With digital PCR, a recently introduced method for CNV analysis, DNA molecules are subjected to limited dilution and separated into nano-scale droplets prior to a PCR assay. Absolute quantitation of copy number can then be performed with high accuracy and sensitivity by determining the number of droplets showing an amplified signal for the target gene. This is the first report of analyses of CYP2D6 and SULT1A1 CNVs using a digital PCR method with blood sample from Japanese subject. Primers and probes were synthesized for the target and reference genes, and copy number calculation was performed using a QX200 Droplet Digital PCR System. Our results showed that the copy numbers in CYP2D6*5 hetero, non-CNV, and CYP2D6xN subjects were 1, 2, and 3 to 4, respectively. In addition, in non-CNV and multiplication subjects, the number of copies for SULT1A1 was 2 and 3 to 6, respectively. We found that the present digital PCR method was useful as well as accurate. In the future, a combined genotyping, allele distinction, and copy number calculation technique will be helpful for analysis of enzymic activity.CYP2D6 and SULT1A1 occasionally show copy number variations (CNVs), with a larger number generally indicating greater enzymic activity. However, those variations are difficult to calculate using standard methods. With digital PCR, a recently introduced method for CNV analysis, DNA molecules are subjected to limited dilution and separated into nano-scale droplets prior to a PCR assay. Absolute quantitation of copy number can then be performed with high accuracy and sensitivity by determining the number of droplets showing an amplified signal for the target gene. This is the first report of analyses of CYP2D6 and SULT1A1 CNVs using a digital PCR method with blood sample from Japanese subject. Primers and probes were synthesized for the target and reference genes, and copy number calculation was performed using a QX200 Droplet Digital PCR System. Our results showed that the copy numbers in CYP2D6*5 hetero, non-CNV, and CYP2D6xN subjects were 1, 2, and 3 to 4, respectively. In addition, in non-CNV and multiplication subjects, the number of copies for SULT1A1 was 2 and 3 to 6, respectively. We found that the present digital PCR method was useful as well as accurate. In the future, a combined genotyping, allele distinction, and copy number calculation technique will be helpful for analysis of enzymic activity. |
| Author | Watanabe, Kazufumi Honma, Hiroyuki Hashimoto, Hiroshi Tadano, Yousuke Kubota, Takahiro Motoi, Yutaro |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/29332892$$D View this record in MEDLINE/PubMed |
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| Cites_doi | 10.1016/S0140-6736(00)03167-6 10.1016/j.ejps.2006.02.008 10.1097/00008571-199508000-00005 10.1124/dmd.30.8.869 10.1016/S0140-6736(77)91430-1 10.1007/BF00541938 10.1016/S0026-895X(25)09721-4 10.1093/hmg/4.12.2251 10.1038/clpt.1986.40 10.1093/carcin/23.11.1897 10.1002/cncr.24111 10.1124/jpet.104.065607 10.7314/APJCP.2012.13.12.6101 10.1073/pnas.90.24.11825 10.1038/clpt.1989.126 10.1124/dmd.108.023242 10.1097/00008571-199804000-00010 10.1097/00008571-199608000-00008 10.1016/S0009-9236(98)90040-6 10.1002/jbt.10048 10.1111/j.1365-2125.1991.tb03939.x 10.1002/cpt1979265584 10.1016/S0006-2952(02)00994-2 10.1093/nar/gkn518 10.1007/BF00316090 10.1038/clpt.1985.194 10.1016/S0027-5107(02)00122-7 10.1007/BF00195139 10.1097/00008571-200211000-00011 10.1006/bbrc.1997.7466 10.1093/annonc/mdn155 10.1093/hmg/ddl468 10.1371/journal.pone.0076648 10.1186/bcr1640 10.1016/S0022-3565(25)10669-1 10.1111/j.1365-2125.1987.tb03080.x 10.1097/00004850-198604000-00002 10.1016/j.cccn.2004.03.002 10.1056/NEJM198212163072505 10.1046/j.1365-2125.2003.01782.x |
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| References | 3. Woosley RL, Roden DM, Dai GH, Wang T, Altenbern D, Oates J, Wilkinson GR. Co-inheritance of the polymorphic metabolism of encainide and debrisoquin. Clin Pharmacol Ther. 1986; 39:282-287. 34. Ohtake E, Kakihara F, Matsumoto N, Ozawa S, Ohno Y, Hasegawa S, Suzuki H, Kubota T. Frequency distribution of phenol sulfotransferase 1A1 activity in platelet cells from healthy Japanese subjects. Eur J Pharm Sci. 2006; 28:272-277. 12. Meyer UA. Pharmacogenetics and adverse drug reactions. Lancet. 2000; 356:1667-1671. 25. Ishiguro A, Kubota T, Sasaki H, Yamada Y, Iga T. Common mutant alleles of CYP2D6 causing the defect of CYP2D6 enzyme activity in a Japanese population. Br J Clin Pharmacol. 2003; 55:414-415. 28. Mitsunaga Y, Kubota T, Ishiguro A, Yamada Y, Sasaki H, Chiba K, Iga T. Frequent occurrence of CYP2D6*10 duplication allele in a Japanese population. Mutat Res. 2002; 505:83-85. 36. Hebbring SJ, Adjei AA, Baer JL, Jenkins GD, Zhang J, Cunningham JM, Schaid DJ, Weinshilboum RM, Thibodeau SN. Human SULT1A1 gene: Copy number differences and functional implications. Hum Mol Genet. 2007; 16:463-470. 16. Sakuyama K, Sasaki T, Ujiie S, Obata K, Mizugaki M, Ishikawa M, Hiratsuka M. Functional characterization of 17 CYP2D6 allelic variants (CYP2D6.2, 10, 14A-B, 18, 27, 36, 39, 47-51, 53-55, and 57). Drug Metab Dispos. 2008; 36:2460-2467. 31. Dalén P, Dahl ML, Bernal RML, Nordin J, Bertilsson L. 10-Hydroxylation of nortriptyline in white persons with 0, 1, 2, 3, and 13 functional CYP2D6 genes. Clin Pharmacol Ther. 1998; 63:444-452. 41. Xu Y, Sun Y, Yao L, Shi L, Wu Y, Ouyang T, Li J, Wang T, Fan Z, Fan T, Lin B, He L, Li P, Xie Y. Association between CYP2D6*10 genotype and survival of breast cancer patients receiving tamoxifen treatment. Ann Oncol Off J Eur Soc Med Oncol. 2008; 19:1423-1429. 2. Baumann P, Jonzier-Perey M, Koeb L, Küpfer A, Tinguely D, Schöpf J. Amitriptyline pharmacokinetics and clinical response: II. Metabolic polymorphism assessed by hydroxylation of debrisoquine and mephenytoin. Int Clin Psychopharmacol. 1986; 1:102-112. 18. Alván G, Bechtel P, Iselius L, Gundert-Remy U. Hydroxylation polymorphisms of debrisoquine and mephenytoin in European populations. Eur J Clin Pharmacol. 1990; 39:533-537. 27. Sachse C, Brockmöller J, Hildebrand M, Müller K, Roots I. Correctness of prediction of the CYP2D6 phenotype confirmed by genotyping 47 intermediate and poor metabolizers of debrisoquine. Pharmacogenetics. 1998; 8:181-185. 38. Qin J, Jones RC, Ramakrishnan R. Studying copy number variations using a nanofluidic platform. Nucleic Acids Res. 2008; 36:e116. 1. Lennard MS, Silas JH, Freestone S, Ramsay LE, Tucker GT, Woods HF. Oxidation phenotype − A major determinant of metoprolol metabolism and response. N Engl J Med. 1982; 307:1558-1560. 24. Sohn DR, Shin SG, Park CW, Kusaka M, Chiba K, Ishizaki T. Metoprolol oxidation polymorphism in a Korean population: Comparison with native Japanese and Chinese populations. Br J Clin Pharmacol. 1991; 32:504-507. 14. Hanioka N, Kimura S, Meyer UA, Gonzalez FJ. The human CYP2D locus associated with a common genetic defect in drug oxidation: a G1934→A base change in intron 3 of a mutant CYP2D6 allele results in an aberrant 3' splice recognition site. Am J Hum Genet. 1990; 47:994-1001. 39. Johansson I, Lundqvist E, Dahl ML, Ingelman-Sundberg M. PCR-based genotyping for duplicated and deleted CYP2D6 genes. Pharmacogenetics. 1996; 6:351-355. 6. Desta Z, Ward BA, Soukhova NV, Flockhart DA. Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: Prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004; 310:1062-1075. 30. Chida M, Ariyoshi N, Yokoi T, Nemoto N, Inaba M, Kinoshita M, Kamataki T. New allelic arrangement CYP2D6*36x2 found in a Japanese poor metabolizer of debrisoquine. Pharmacogenetics. 2002; 12:659-662. 42. Gjerde J, Hauglid M, Breilid H, Lundgren S, Varhaug JE, Kisanga ER, Mellgren G, Steen VM, Lien EA. Effects of CYP2D6 and SULT1A1 genotypes including SULT1A1 gene copy number on tamoxifen metabolism. Ann Oncol Off J Eur Soc. Med Oncol. 2008; 19:56-61. 29. Ishiguro A, Kubota T, Ishikawa H, Iga T. Metabolic activity of dextromethorphan O-demethylation in healthy Japanese volunteers carrying duplicated CYP2D6 genes: Duplicated allele of CYP2D6*10 does not increase CYP2D6 metabolic activity. Clin Chim Acta. 2004; 344:201-204. 7. Daly AK. Molecular basis of polymorphic drug metabolism. J Mol Med. 1995; 73:539-553. 10. Johansson I, Oscarson M, Yue QY, Bertilsson L, Sjöqvist F, Ingelman-Sundberg M. Genetic analysis of the Chinese cytochrome P4502D locus: Characterization of variant CYP2D6 genes present in subjects with diminished capacity for debrisoquine hydroxylation. Mol Pharmacol. 1994; 46:452-459. 17. Ishiguro A, Kubota T, Soya Y, Sasaki H, Yagyu O, Takarada Y, Iga T. High-throughput detection of multiple genetic polymorphisms influencing drug metabolism with mismatch primers in allele-specific polymerase chain reaction. Anal. Biochem. 2005; 337:256-261. 20. Woolhouse NM, Andoh B, Mahgoub A, Sloan TP, Idle JR, Smith RL. Debrisoquin hydroxylation polymorphism among Ghanaians and Caucasians. Clin Pharmacol Ther. 1979; 26:584-591. 8. Mahgoub A, Idle JR, Dring LG, Lancaster R, Smith RL. Polymorphic hydroxylation of Debrisoquine in man. Lancet. 1977; 2:584-586. 46. Motamedi S, Majidzadeh K, Mazaheri M, Anbiaie R, Mortazavizadeh SM, Esmaeili R. Tamoxifen resistance and CYP2D6 copy numbers in breast cancer patients. Asian Pac J Cancer Prev. 2012; 13:6101-6104. 4. Crewe HK, Notley LM, Wunsch RM, Lennard MS, Gillam EMJ. Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: Formation of the 4-hydroxy, 4'-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab Dispos. 2002; 30:869-874. 21. Nakamura K, Goto F, Ray WA, McAllister CB, Jacqz E, Wilkinson GR, Branch RA. Interethnic differences in genetic polymorphism of debrisoquin and mephenytoin hydroxylation between Japanese and Caucasian populations. Clin Pharmacol Ther. 1985; 38:402-408. 23. Horai Y, Nakano M, Ishizaki T, Ishikawa K, Zhou HH, Zhou BI, Liao CL, Zhang LM. Metoprolol and mephenytoin oxidation polymorphisms in Far Eastern Oriental subjects: Japanese versus mainland Chinese. Clin Pharmacol Ther. 1989; 46:198-207. 5. Boocock DJ, Brown K, Gibbs AH, Sanchez E, Turteltaub KW, White IN. Identification of human CYP forms involved in the activation of tamoxifen and irreversible binding to DNA. Carcinogenesis. 2002; 23:1897-1901. 45. Lum DWK, Perel P, Hingorani AD, Holmes MV. CYP2D6 genotype and tamoxifen response for breast cancer: A systematic review and meta-analysis. PLoS One. 2013; 8:e76648. 32. Nishiyama T, Ogura K, Nakano H, Ohnuma T, Kaku T, Hiratsuka A, Muro K, Watabe T. Reverse geometrical selectivity in glucuronidation and sulfation of cis- and trans-4-hydroxytamoxifens by human liver UDPglucuronosyltransferases and sulfotransferases. Biochem Pharmacol. 2002; 63:1817-1830. 43. Wegman P, Elingarami S, Carstensen J, Stal O, Nordenskjold B, Wingren S. Genetic variants of CYP3A5, CYP2D6, SULT1A1, UGT2B15 and tamoxifen response in postmenopausal patients with breast cancer. Breast Cancer Res. 2007; 9:R7. 13. The Human Cytochrome P450 (CYP) Allele Nomenclature Database. https://www.cypalleles.ki.se/cyp2d6.htm (accessed October 25, 2017). 15. Steen VM, Molven A, Aarskog NK, Gulbrandsen AK. Homologous unequal cross-over involving a 2.8 kb direct repeat as a mechanism for the generation of allelic variants of human cytochrome P450 CYP2D6 gene. Hum Mol Genet. 1995; 4:2251-2257. 26. Dahl ML, Johansson I, Bertilsson L, Ingelman-Sundberg M, Sjöqvist F. Ultrarapid hydroxylation of debrisoquine in a Swedish population. Analysis of the molecular genetic basis. J Pharmacol Exp Ther. 1995; 274:516-520. 44. Okishiro M, Taguchi T, Jin KS, Shimazu K, Tamaki Y, Noguchi S. Genetic polymorphisms of CYP2D6*10 and CYP2C19*2, *3 are not associated with prognosis, endometrial thickness, or bone mineral density in Japanese breast cancer patients treated with adjuvant tamoxifen. Cancer. 2009; 115:952-961. 37. Yu X, Kubota T, Dhakal I, Hasegawa S, Williams S, Ozawa S, Kadlubar S. Copy number variation in sulfotransferase isoform 1A1 (SULT1A1) is significantly associated with enzymatic activity in Japanese subjects. Pharmgenomics Pers Med. 2013; 6:19-24. 19. Lou YC, Ying L, Bertilsson L, Sjöqvist F. Low frequency of slow debrisoquine hydroxylation in a native Chinese population. Lancet. 1987; 2:852-853. 9. Küpfer A, Preisig R. Pharmacogenetics of mephenytoin: A new drug hydroxylation polymorphism in man. Eur J Clin Pharmacol. 1984; 26:753-759. 11. Johansson I, Lundqvist E, Bertilsson L, Dahl ML, Sjöqvist F, Ingelman-Sundberg M. Inherited amplification of an active gene in the cytochrome P450 CYP2D locus as a cause of ultrarapid metabolism of debrisoquine. Proc Natl Acad Sci U S A. 1993; 90:11825-11829. 22. Ishizaki T, Eichelbaum M, Horai Y, Hashimoto K, Chiba K, Dengler HJ. Evidence for polymorphic oxidation of sparteine in Japanese subjects. Br J Clin Pharmacol. 1987; 23:482-485. 33. Chen G, Yin S, Maiti S, Shao X. 4-Hydroxytamoxifen sulfation metabolism. J Biochem Mol Toxicol. 2002; 16:279-285. 40. Steen VM, Andreassen OA, Daly AK, Tefre T, Børresen AL, Idle JR, Gulbrandsen AK. Detection of the poor metabolizer-associated CYP2D6(D) gene deletion allele by long-PCR technology. Pharmacogenetics. 1995; 5:215-223. 35. Raftogianis RB, Wood TC, Otterness DM, Van Loon JA, Weinshilboum RM. Phenol sulfotransferase pharmacogenetics in humans: Association of common SULT1A1 alleles with TS PST phenotype. Biochem Biophys Res Commun. 1997; 239:298-304. 22 44 23 45 24 46 25 26 27 28 29 30 31 10 32 11 33 12 34 13 35 14 36 15 37 16 38 17 39 18 19 1 2 3 4 5 6 7 8 9 40 41 20 42 21 43 |
| References_xml | – reference: 32. Nishiyama T, Ogura K, Nakano H, Ohnuma T, Kaku T, Hiratsuka A, Muro K, Watabe T. Reverse geometrical selectivity in glucuronidation and sulfation of cis- and trans-4-hydroxytamoxifens by human liver UDPglucuronosyltransferases and sulfotransferases. Biochem Pharmacol. 2002; 63:1817-1830. – reference: 42. Gjerde J, Hauglid M, Breilid H, Lundgren S, Varhaug JE, Kisanga ER, Mellgren G, Steen VM, Lien EA. Effects of CYP2D6 and SULT1A1 genotypes including SULT1A1 gene copy number on tamoxifen metabolism. Ann Oncol Off J Eur Soc. Med Oncol. 2008; 19:56-61. – reference: 40. Steen VM, Andreassen OA, Daly AK, Tefre T, Børresen AL, Idle JR, Gulbrandsen AK. Detection of the poor metabolizer-associated CYP2D6(D) gene deletion allele by long-PCR technology. Pharmacogenetics. 1995; 5:215-223. – reference: 7. Daly AK. Molecular basis of polymorphic drug metabolism. J Mol Med. 1995; 73:539-553. – reference: 18. Alván G, Bechtel P, Iselius L, Gundert-Remy U. Hydroxylation polymorphisms of debrisoquine and mephenytoin in European populations. Eur J Clin Pharmacol. 1990; 39:533-537. – reference: 34. Ohtake E, Kakihara F, Matsumoto N, Ozawa S, Ohno Y, Hasegawa S, Suzuki H, Kubota T. Frequency distribution of phenol sulfotransferase 1A1 activity in platelet cells from healthy Japanese subjects. Eur J Pharm Sci. 2006; 28:272-277. – reference: 27. Sachse C, Brockmöller J, Hildebrand M, Müller K, Roots I. Correctness of prediction of the CYP2D6 phenotype confirmed by genotyping 47 intermediate and poor metabolizers of debrisoquine. Pharmacogenetics. 1998; 8:181-185. – reference: 19. Lou YC, Ying L, Bertilsson L, Sjöqvist F. Low frequency of slow debrisoquine hydroxylation in a native Chinese population. Lancet. 1987; 2:852-853. – reference: 45. Lum DWK, Perel P, Hingorani AD, Holmes MV. CYP2D6 genotype and tamoxifen response for breast cancer: A systematic review and meta-analysis. PLoS One. 2013; 8:e76648. – reference: 4. Crewe HK, Notley LM, Wunsch RM, Lennard MS, Gillam EMJ. Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: Formation of the 4-hydroxy, 4'-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab Dispos. 2002; 30:869-874. – reference: 17. Ishiguro A, Kubota T, Soya Y, Sasaki H, Yagyu O, Takarada Y, Iga T. High-throughput detection of multiple genetic polymorphisms influencing drug metabolism with mismatch primers in allele-specific polymerase chain reaction. Anal. Biochem. 2005; 337:256-261. – reference: 39. Johansson I, Lundqvist E, Dahl ML, Ingelman-Sundberg M. PCR-based genotyping for duplicated and deleted CYP2D6 genes. Pharmacogenetics. 1996; 6:351-355. – reference: 13. The Human Cytochrome P450 (CYP) Allele Nomenclature Database. https://www.cypalleles.ki.se/cyp2d6.htm (accessed October 25, 2017). – reference: 44. Okishiro M, Taguchi T, Jin KS, Shimazu K, Tamaki Y, Noguchi S. Genetic polymorphisms of CYP2D6*10 and CYP2C19*2, *3 are not associated with prognosis, endometrial thickness, or bone mineral density in Japanese breast cancer patients treated with adjuvant tamoxifen. Cancer. 2009; 115:952-961. – reference: 35. Raftogianis RB, Wood TC, Otterness DM, Van Loon JA, Weinshilboum RM. Phenol sulfotransferase pharmacogenetics in humans: Association of common SULT1A1 alleles with TS PST phenotype. Biochem Biophys Res Commun. 1997; 239:298-304. – reference: 2. Baumann P, Jonzier-Perey M, Koeb L, Küpfer A, Tinguely D, Schöpf J. Amitriptyline pharmacokinetics and clinical response: II. Metabolic polymorphism assessed by hydroxylation of debrisoquine and mephenytoin. Int Clin Psychopharmacol. 1986; 1:102-112. – reference: 46. Motamedi S, Majidzadeh K, Mazaheri M, Anbiaie R, Mortazavizadeh SM, Esmaeili R. Tamoxifen resistance and CYP2D6 copy numbers in breast cancer patients. Asian Pac J Cancer Prev. 2012; 13:6101-6104. – reference: 36. Hebbring SJ, Adjei AA, Baer JL, Jenkins GD, Zhang J, Cunningham JM, Schaid DJ, Weinshilboum RM, Thibodeau SN. Human SULT1A1 gene: Copy number differences and functional implications. Hum Mol Genet. 2007; 16:463-470. – reference: 14. Hanioka N, Kimura S, Meyer UA, Gonzalez FJ. The human CYP2D locus associated with a common genetic defect in drug oxidation: a G1934→A base change in intron 3 of a mutant CYP2D6 allele results in an aberrant 3' splice recognition site. Am J Hum Genet. 1990; 47:994-1001. – reference: 3. Woosley RL, Roden DM, Dai GH, Wang T, Altenbern D, Oates J, Wilkinson GR. Co-inheritance of the polymorphic metabolism of encainide and debrisoquin. Clin Pharmacol Ther. 1986; 39:282-287. – reference: 31. Dalén P, Dahl ML, Bernal RML, Nordin J, Bertilsson L. 10-Hydroxylation of nortriptyline in white persons with 0, 1, 2, 3, and 13 functional CYP2D6 genes. Clin Pharmacol Ther. 1998; 63:444-452. – reference: 26. Dahl ML, Johansson I, Bertilsson L, Ingelman-Sundberg M, Sjöqvist F. Ultrarapid hydroxylation of debrisoquine in a Swedish population. Analysis of the molecular genetic basis. J Pharmacol Exp Ther. 1995; 274:516-520. – reference: 10. Johansson I, Oscarson M, Yue QY, Bertilsson L, Sjöqvist F, Ingelman-Sundberg M. Genetic analysis of the Chinese cytochrome P4502D locus: Characterization of variant CYP2D6 genes present in subjects with diminished capacity for debrisoquine hydroxylation. Mol Pharmacol. 1994; 46:452-459. – reference: 12. Meyer UA. Pharmacogenetics and adverse drug reactions. Lancet. 2000; 356:1667-1671. – reference: 1. Lennard MS, Silas JH, Freestone S, Ramsay LE, Tucker GT, Woods HF. Oxidation phenotype − A major determinant of metoprolol metabolism and response. N Engl J Med. 1982; 307:1558-1560. – reference: 21. Nakamura K, Goto F, Ray WA, McAllister CB, Jacqz E, Wilkinson GR, Branch RA. Interethnic differences in genetic polymorphism of debrisoquin and mephenytoin hydroxylation between Japanese and Caucasian populations. Clin Pharmacol Ther. 1985; 38:402-408. – reference: 41. Xu Y, Sun Y, Yao L, Shi L, Wu Y, Ouyang T, Li J, Wang T, Fan Z, Fan T, Lin B, He L, Li P, Xie Y. Association between CYP2D6*10 genotype and survival of breast cancer patients receiving tamoxifen treatment. Ann Oncol Off J Eur Soc Med Oncol. 2008; 19:1423-1429. – reference: 8. Mahgoub A, Idle JR, Dring LG, Lancaster R, Smith RL. Polymorphic hydroxylation of Debrisoquine in man. Lancet. 1977; 2:584-586. – reference: 11. Johansson I, Lundqvist E, Bertilsson L, Dahl ML, Sjöqvist F, Ingelman-Sundberg M. Inherited amplification of an active gene in the cytochrome P450 CYP2D locus as a cause of ultrarapid metabolism of debrisoquine. Proc Natl Acad Sci U S A. 1993; 90:11825-11829. – reference: 16. Sakuyama K, Sasaki T, Ujiie S, Obata K, Mizugaki M, Ishikawa M, Hiratsuka M. Functional characterization of 17 CYP2D6 allelic variants (CYP2D6.2, 10, 14A-B, 18, 27, 36, 39, 47-51, 53-55, and 57). Drug Metab Dispos. 2008; 36:2460-2467. – reference: 29. Ishiguro A, Kubota T, Ishikawa H, Iga T. Metabolic activity of dextromethorphan O-demethylation in healthy Japanese volunteers carrying duplicated CYP2D6 genes: Duplicated allele of CYP2D6*10 does not increase CYP2D6 metabolic activity. Clin Chim Acta. 2004; 344:201-204. – reference: 38. Qin J, Jones RC, Ramakrishnan R. Studying copy number variations using a nanofluidic platform. Nucleic Acids Res. 2008; 36:e116. – reference: 24. Sohn DR, Shin SG, Park CW, Kusaka M, Chiba K, Ishizaki T. Metoprolol oxidation polymorphism in a Korean population: Comparison with native Japanese and Chinese populations. Br J Clin Pharmacol. 1991; 32:504-507. – reference: 9. Küpfer A, Preisig R. Pharmacogenetics of mephenytoin: A new drug hydroxylation polymorphism in man. Eur J Clin Pharmacol. 1984; 26:753-759. – reference: 25. Ishiguro A, Kubota T, Sasaki H, Yamada Y, Iga T. Common mutant alleles of CYP2D6 causing the defect of CYP2D6 enzyme activity in a Japanese population. Br J Clin Pharmacol. 2003; 55:414-415. – reference: 22. Ishizaki T, Eichelbaum M, Horai Y, Hashimoto K, Chiba K, Dengler HJ. Evidence for polymorphic oxidation of sparteine in Japanese subjects. Br J Clin Pharmacol. 1987; 23:482-485. – reference: 23. Horai Y, Nakano M, Ishizaki T, Ishikawa K, Zhou HH, Zhou BI, Liao CL, Zhang LM. Metoprolol and mephenytoin oxidation polymorphisms in Far Eastern Oriental subjects: Japanese versus mainland Chinese. Clin Pharmacol Ther. 1989; 46:198-207. – reference: 30. Chida M, Ariyoshi N, Yokoi T, Nemoto N, Inaba M, Kinoshita M, Kamataki T. New allelic arrangement CYP2D6*36x2 found in a Japanese poor metabolizer of debrisoquine. Pharmacogenetics. 2002; 12:659-662. – reference: 15. Steen VM, Molven A, Aarskog NK, Gulbrandsen AK. Homologous unequal cross-over involving a 2.8 kb direct repeat as a mechanism for the generation of allelic variants of human cytochrome P450 CYP2D6 gene. Hum Mol Genet. 1995; 4:2251-2257. – reference: 6. Desta Z, Ward BA, Soukhova NV, Flockhart DA. Comprehensive evaluation of tamoxifen sequential biotransformation by the human cytochrome P450 system in vitro: Prominent roles for CYP3A and CYP2D6. J Pharmacol Exp Ther. 2004; 310:1062-1075. – reference: 37. Yu X, Kubota T, Dhakal I, Hasegawa S, Williams S, Ozawa S, Kadlubar S. Copy number variation in sulfotransferase isoform 1A1 (SULT1A1) is significantly associated with enzymatic activity in Japanese subjects. Pharmgenomics Pers Med. 2013; 6:19-24. – reference: 33. Chen G, Yin S, Maiti S, Shao X. 4-Hydroxytamoxifen sulfation metabolism. J Biochem Mol Toxicol. 2002; 16:279-285. – reference: 20. Woolhouse NM, Andoh B, Mahgoub A, Sloan TP, Idle JR, Smith RL. Debrisoquin hydroxylation polymorphism among Ghanaians and Caucasians. Clin Pharmacol Ther. 1979; 26:584-591. – reference: 28. Mitsunaga Y, Kubota T, Ishiguro A, Yamada Y, Sasaki H, Chiba K, Iga T. Frequent occurrence of CYP2D6*10 duplication allele in a Japanese population. Mutat Res. 2002; 505:83-85. – reference: 43. Wegman P, Elingarami S, Carstensen J, Stal O, Nordenskjold B, Wingren S. Genetic variants of CYP3A5, CYP2D6, SULT1A1, UGT2B15 and tamoxifen response in postmenopausal patients with breast cancer. Breast Cancer Res. 2007; 9:R7. – reference: 5. Boocock DJ, Brown K, Gibbs AH, Sanchez E, Turteltaub KW, White IN. Identification of human CYP forms involved in the activation of tamoxifen and irreversible binding to DNA. Carcinogenesis. 2002; 23:1897-1901. – ident: 12 doi: 10.1016/S0140-6736(00)03167-6 – ident: 34 doi: 10.1016/j.ejps.2006.02.008 – ident: 40 doi: 10.1097/00008571-199508000-00005 – ident: 4 doi: 10.1124/dmd.30.8.869 – ident: 8 doi: 10.1016/S0140-6736(77)91430-1 – ident: 9 doi: 10.1007/BF00541938 – ident: 10 doi: 10.1016/S0026-895X(25)09721-4 – ident: 15 doi: 10.1093/hmg/4.12.2251 – ident: 3 doi: 10.1038/clpt.1986.40 – ident: 5 doi: 10.1093/carcin/23.11.1897 – ident: 44 doi: 10.1002/cncr.24111 – ident: 6 doi: 10.1124/jpet.104.065607 – ident: 37 – ident: 46 doi: 10.7314/APJCP.2012.13.12.6101 – ident: 11 doi: 10.1073/pnas.90.24.11825 – ident: 23 doi: 10.1038/clpt.1989.126 – ident: 14 – ident: 16 doi: 10.1124/dmd.108.023242 – ident: 27 doi: 10.1097/00008571-199804000-00010 – ident: 39 doi: 10.1097/00008571-199608000-00008 – ident: 31 doi: 10.1016/S0009-9236(98)90040-6 – ident: 33 doi: 10.1002/jbt.10048 – ident: 24 doi: 10.1111/j.1365-2125.1991.tb03939.x – ident: 17 – ident: 20 doi: 10.1002/cpt1979265584 – ident: 42 – ident: 32 doi: 10.1016/S0006-2952(02)00994-2 – ident: 38 doi: 10.1093/nar/gkn518 – ident: 18 doi: 10.1007/BF00316090 – ident: 21 doi: 10.1038/clpt.1985.194 – ident: 28 doi: 10.1016/S0027-5107(02)00122-7 – ident: 7 doi: 10.1007/BF00195139 – ident: 19 – ident: 30 doi: 10.1097/00008571-200211000-00011 – ident: 13 – ident: 35 doi: 10.1006/bbrc.1997.7466 – ident: 41 doi: 10.1093/annonc/mdn155 – ident: 36 doi: 10.1093/hmg/ddl468 – ident: 45 doi: 10.1371/journal.pone.0076648 – ident: 43 doi: 10.1186/bcr1640 – ident: 26 doi: 10.1016/S0022-3565(25)10669-1 – ident: 22 doi: 10.1111/j.1365-2125.1987.tb03080.x – ident: 2 doi: 10.1097/00004850-198604000-00002 – ident: 29 doi: 10.1016/j.cccn.2004.03.002 – ident: 1 doi: 10.1056/NEJM198212163072505 – ident: 25 doi: 10.1046/j.1365-2125.2003.01782.x |
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| Title | Digital PCR for determination of cytochrome P450 2D6 and sulfotransferase 1A1 gene copy number variations |
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