PXR, CAR and HNF4α genotypes and their association with pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin in Asian patients

Pharmacogenomics Journal

Volumn 8, Issue 2, 2008, Pages 139-146

  Hor, S Y ^a   Lee, S C ^b   Wong, C I ^b   Lim, Y W ^b   Lim, R C ^b   Wang, L Z ^b   Fan, L ^a   Guo, J Y ^b   Lee, H S ^a   Goh, B C ^b   Tan, T ^a  

^a NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^b NATIONAL UNIVERSITY HOSPITAL   (Singapore)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE; CONSTITUTIVE ANDROSTANE RECEPTOR; CYTOCHROME P450 3A; CYTOSINE; DOCETAXEL; DOXORUBICIN; HEPATOCYTE NUCLEAR FACTOR 4ALPHA; METHIONINE; MULTIDRUG RESISTANCE PROTEIN 1; PREGNANE X RECEPTOR; PROLINE; VALINE; ANTINEOPLASTIC AGENT; ANTINEOPLASTIC ANTIBIOTIC; CELL RECEPTOR; CYP3A5 PROTEIN, HUMAN; CYTOCHROME P450; HEPATOCYTE NUCLEAR FACTOR 4; HNF4A PROTEIN, HUMAN; STEROID RECEPTOR; TAXOID; TRANSCRIPTION FACTOR; UNCLASSIFIED DRUG;

5' UNTRANSLATED REGION; ADULT; AGED; ANALYSIS OF VARIANCE; ARTICLE; ASIAN; BLOOD TOXICITY; BONE MARROW SUPPRESSION; BREAST CANCER; CHINESE; CONTROLLED STUDY; CORRELATION ANALYSIS; DRUG BLOOD LEVEL; DRUG CLEARANCE; ETHNIC DIFFERENCE; ETHNIC GROUP; GENE FREQUENCY; GENETIC ASSOCIATION; GENETIC POLYMORPHISM; GENETIC VARIABILITY; GENOTYPE; HUMAN; INDIAN; LEUKOPENIA; MAJOR CLINICAL STUDY; NEUTROPENIA; NEUTROPHIL; NUCLEOTIDE SEQUENCE; PHARMACODYNAMICS; POST HOC ANALYSIS; PRIORITY JOURNAL; TRANSCRIPTION REGULATION; WILD TYPE; BREAST TUMOR; CHEMICALLY INDUCED DISORDER; CHINA; CLINICAL TRIAL; COMPARATIVE STUDY; CONTROLLED CLINICAL TRIAL; DRUG EFFECT; ENZYMOLOGY; ETHNOLOGY; EXON; FEMALE; GENE EXPRESSION REGULATION; GENETICS; INDIA; MALAYSIA; METABOLISM; MIDDLE AGED; RANDOMIZED CONTROLLED TRIAL; SINGAPORE; THROMBOCYTE; TIME; TREATMENT OUTCOME;

5' UNTRANSLATED REGIONS; ADULT; AGED; ANTIBIOTICS, ANTINEOPLASTIC; ANTINEOPLASTIC AGENTS, PHYTOGENIC; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; ASIAN CONTINENTAL ANCESTRY GROUP; BLOOD PLATELETS; BREAST NEOPLASMS; CHINA; CYTOCHROME P-450 ENZYME SYSTEM; DOXORUBICIN; EXONS; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; GENE FREQUENCY; GENOTYPE; HEPATOCYTE NUCLEAR FACTOR 4; HUMANS; INDIA; MALAYSIA; MIDDLE AGED; NEUTROPENIA; POLYMORPHISM, GENETIC; RECEPTORS, CYTOPLASMIC AND NUCLEAR; RECEPTORS, STEROID; SINGAPORE; TAXOIDS; TIME FACTORS; TRANSCRIPTION FACTORS; TREATMENT OUTCOME;

EID: 40949155833     PISSN: 1470269X     EISSN: 14731150     Source Type: Journal    
DOI: 10.1038/sj.tpj.6500478     Document Type: Article

References (34)

1. Hesselink DA, van Schalk RH, van der Heiden JP, van der Werf M, Gregoor PJ, Linclemans J et al. Genetic polymorphismsof the CYP3A4, CYP3A5, and MDR-1 genes and pharmacokinetics of the calcineurin inhibitors cyclosporine and tacrolimus. Clin Pharmacol Ther 2003; 74: 245-254.
2. Xie HG, Wood AJ, Kim RB, Stein CM, Wilkinson GR. Genetic variability in CYP3A5 and its possible consequences. Pharmacogenomics 2004; 5 243-272.
3. Kajinami K, Brousseau ME, Ordovas JM, Schaefer EJ. CYP3A4 genotypes and plasma lipoprotein levels before and after treatment with atorvastatin in primary hypercholesterolemia. Am J Cardiol 2004; 93: 104-107.
4. Ozdemir V, Kalowa W, Tang BK, Paterson AD, Walker SE, Endrenyi L et al. Evaluation of the genetic component of variability in CYP3A4 activity: A repeated drug administration method. Pharmacogenetics 2000; 10: 373-388.
5. Sakaeda T, Nakamura T, Okumura K. Pharmacogenetics of MDR1 and its impact on the pharmacokinetics and pharmacodynamics of drugs. Pharmacogenomics 2003; 4: 397-410.
6. Yi SY, Hong KS, Lim HS, Chung JY, Oh DS, Kim JR et al. A variant 2677A allele of the MDR1 gene affects fexofenadine disposition. Clin Pharmacol Ther 2004; 76: 418-427.
7. Kim RB, Leake BF, Choo EF, Dresser GK, Kubba SV, Schwarz UI et al. Identification of functionally variant mdr1 alleles among European Americans and African Americans. Clin Pharmacol Ther 2001; 70 189-199.
8. Goh BC, Lee SC, Wang LZ, Fan L, Guo JY, Lamba J et al. Explaining interindividual variability of docetaxel pharmacokinetics and pharmacodynamics in Asians through phenotyping and genotyping strategies. J Clin Oncol 2002; 20: 3683-3690.
9. Kliewer SA, Moore JT, Wade L, Staudinger JL, Watson MA, Jones SA et al. An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell 1998; 92: 73-82.
10. Goodwin B, Redinbo MR, Kliewer SA. Regulation of cyp3a gene transcription by the pregnane X receptor. Annu Rev Pharmacol Toxicol 2002; 42: 1-23.
11. Kliewer SA, Goodwin B, Willson TM. The nuclear pregnane X receptor: A key regulator of xenobiotic metabolism. Endocr Rev 2002; 23: 687-702.
12. Willson TM, Kliewer SA. PXR, CAR and drug metabolism. Nat Rev Drug Discov 2002; 1: 259-266.
13. Tirona RG, Lee W, Leake BF, Lan LB, Cline CB, Lamba V et al. The orphan nuclear receptor HNF4alpha determines PXR- and CAR-mediated xenobiotic induction of CYP3A4. Nat Med 2003; 9: 220-224.
14. Wang H, LeCluyse EL. Role of orphan nuclear receptors in the regulation of drug-metabolising enzymes. Clin Phormacokinet 2003; 42: 1331-1357.
15. Jiang G, Sladek FM. The DNA binding domain of hepatocyte nuclear factor 4 mediates cooperative, specific binding to DNA and heterodimerization with the retinoid X receptor alpha. J Biol Chem 1997; 272: 1218-1225.
16. Jover R, Bort R, Gomez-Lechon MJ, Castell JV. Cytochrome P450 regulation by hepatocyte nuclear factor 4 in human hepatocytes: A study using adenovirus-mediated antisense targeting. Hepatology 2001; 33 668-675.
17. Lausen J, Thomas H, Lemm I, Bulman M, Borgschulze M, Lingott A et al Naturally occurring mutations in the human HNF4alpha gene impair the function of the transcription factor to a varying degree. Nucleic Acids Res 2000; 28: 430-437.
18. Lamba J, Lamba V, Schuetz E. Genetic variants of PXR (NR112) and CAR (NR113) and their implications in drug metabolism and pharmacogenetics. Curr Drug Metab 2005; 6: 369-383.
19. Andersen A,. Holte H, Slordal L. Pharmacokinetics and metabolism of doxorubicin after short-term infusions in lymphoma patients. Cancer Chemother Pharmacol 1999; 44: 422-426.
20. Clarke SJ, Rivory LP. Clinical pharmacokinetics of docetaxel. Clin Pharmacokinet 1999; 36: 99-114.
21. Zhang J, Kuehl P, Green. ED, Touchman JW, Watkins PB, Daly A et al The human pregnane X receptor: Genomic structure and identification and functional characterization of natural allelic variants. Pharmacogenetics 2001; 11: 555-572.
22. Bosch TM, Deenen M, Pruntel R, Smits PH, Schellens JH, Beijnen JH et al. Screening for polymorphisms in the PXR gene in a Dutch population. Eur J Clin Pharmacol 2006; 62: 395-399.
23. Koyano S, Kurose K, Ozawa S, Saeki M, Nakajima Y, Hasegawa R et al Eleven novel single nucleotide polymorphisms in the NR112 (PXR) gene, four of which induce non-synonymous amino acid alterations. Drug Metab Pharmacokinet 2002; 17: 561-565.
24. Lee SC, Ng SS, Oldenburg J, Chong PY, Rost S, Guo JY et al. Interethnic variability of warfarin maintenance requirement is explained by VKORC1 genotype in an Asian population. Clin Pharmacol Ther 2006; 79: 197-205.
25. Ek J, Rose CS, Jensen DP, Glumer C, Borch-Johnsen K, Jorgensen T et al. The functional Thr130lle and Val255Met polymorphisms of the hepatocyte nuclear factor-4alpha (HNF4A): Gene associations With type 2 diabetes or altered beta-cell function among danes. J Clin Endocrinol Metab 2005; 90: 3054-3059.
26. Pruhova 5, Ek J, Lebl J, Sumnik Z, Saudek F, Andel M et al. Genetic epidemiology of MODY in the Czech republic: New mutations in the MODY genes HNF-4alpha, GCK and HNF-1alpha. Diabetologia 2003; 46: 291-295.
27. Green VJ, Kokkotou E, Ladias JA. Critical structural elements and multitarget protein interactions of the transcriptional activator AF-1 of hepatocyte nuclear factor 4. J Biol Chem 1998; 273: 29950-29957.
28. Eeckhoute J, Formstecher P, Laine B. Maturity-onset diabetes of the young Type 1 (MODY1)-associated mutations R154X and E2760 in hepatocyte nuclear factor 4alpha (HNF4alpha) gene impair recruitment of p300, a key transcriptional co-activator. Mol Endocrinol 2001; 15: 1200-1210.
29. Eeckhoute J, Moerman E, Bouckenooghe T, Lukoviak B, Pattou F, Formstecher P et al. Hepatocyte nuclear factor 4 alpha Isoforms originated from the P1 promoter are expressed in human pancreatic beta-cells and exhibit stronger transcriptional potentials than P2 promoter-driven isoforms. Endocrinology 2003; 144: 1686-1694.
30. Kistanova E, Dell H, Tsantili P, Falvey. E, Cladaras C, Hadzopoulou-Cladaras M. The activation function-1 of hepatocyte nuclear factor-4 is an acidic activator that mediates interactions through bulky hydrophobic residues. Biochem J 2001; 356: 635-642.
31. Zhu Q, Yamagata K, Miura A, Shihara N, Horikawa Y, Takeda J et al. T130l mutation in HNF-4alpha gene is a loss-of-function mutation in hepatocytes and is associated with late-onset Type 2 diabetes mellitus in Japanese subjects. Diabetologio 2003; 46: 567-573.
32. Bosch TM, Huitema AD, Doodeman VD, Jansen R, Witteveen E, Smit WM et al. Pharmacogenetic screening of CYP3A and ABCB1 in relation to population pharmacokinetics of docetaxel. Clin Cancer Res 2006; 12: 5786-5793.
33. Guitton J, Cohen S, Tranchand B, Vignal B, Droz JP, Guillaumont M et al. Quantification of docetaxel and its main metabolites in human plasma by liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom 2005; 19: 2419-2426.
34. Andersen A, Warren DJ, Slordal L. A sensitive and simple high-performance liquid chromatographic method for the determination of doxorubicin and its metabolites in plasma. Ther Drug Monit 1993; 15: 455-461.