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Published in:

01-01-2006 | Review Article

Significance of the Minor Cytochrome P450 3A Isoforms

Author: Dr Ann K. Daly

Published in: Clinical Pharmacokinetics | Issue 1/2006

Abstract

Cytochrome P450 (CYP) 3A4 is responsible for most CYP3A-mediated drug metabolism but the minor isoforms CYP3A5, CYP3A7 and CYP3A43 also contribute. CYP3A5 is the best studied of the minor CYP3A isoforms. It is well established that only approximately 20% of livers express CYP3A5. The most common reason for the absence of expression is a splice site mutation. The frequency of variant alleles shows interethnic differences, with the wild-type CYP3A5* allele more common in Africans than Caucasians and Asians. In individuals who express CYP3A5, the percentage contributed to total hepatic CYP3A by this isoform is still unclear, with estimates ranging from 17% to 50%. CYP3A5 is also expressed in a range of extrahepatic tissues. Only limited information is available on the regulation of CYP3A5 expression but it appears to be inducible via the glucocorticoid receptor, pregnane X receptor and constitutive androstane receptor-β, as for CYP3A4. Although information on the substrate specificity of CYP3A5 is limited compared with CYP3A4, there have been a number of recent pharmacokinetic studies on a small range of substrates in individuals of known genotype to investigate the contribution of CYP3A5. In the case of midazolam, Ciclosporin, nifedipine and docetaxel, clearance by individuals with a CYP3A5-expressing genotype did not differ from that for nonexpressors, but in the case of tacrolimus, eight independent studies have demonstrated faster clearance by those carrying one or two CYP3A5*1 alleles. This may reflect faster turnover of tacrolimus by CYP3A5 than the other substrates. CYP3A5 genotype may affect cancer susceptibility. Certain combined CYP3A4/CYP3A5 haplotypes show differential susceptibility to prostate cancer and there is a nonsignificant increase in the risk of small-cell lung cancer for a CYP3A5* 1/*1 genotype. Females positive for CYP3A5*1 appear to reach puberty earlier, which may affect breast cancer risk. CYP3A5*1 homozygotes may have higher systolic blood pressure.

CYP3A7 is predominantly expressed in fetal liver but is also found in some adult livers and extrahepatically. The molecular basis for expression in adult liver relates to upstream polymorphisms, which appear to increase homology to CYP3A4 and make regulation of expression more similar. CYP3A7 has a specific role in hydroxylation of retinoic acid and 16α-hydroxylation of steroids, and is therefore of relevance both to normal development and carcinogenesis.

CYP3A43 is the most recently discovered CYP3A isoform. In addition to a low level of expression in liver, it is expressed in prostate and testis. Its substrate specificity is currently unclear. Polymorphisms predicting absence of active enzyme have been identified.

Rendic S. Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev 2002; 34(1–2): 83–448PubMedCrossRef

Lamba JK, Lin YS, Schuetz EG, et al. Genetic contribution to variable human CYP3A-mediated metabolism. Adv Drug Deliv Rev 2002; 54(10): 1271–94PubMedCrossRef

Molowa DT, Schuetz EG, Wrighton SA, et al. Complete cDNA sequence of a cytochrome P-450 inducible by glucocorticoids in human liver. Proc Natl Acad Sci U S A 1986; 83(14): 5311–5PubMedCrossRef

Beaune PH, Umbenhauer DR, Bork RW, et al. Isolation and sequence determination of a cDNA clone related to human cytochrome P-450 nifedipine oxidase. Proc Natl Acad Sci U S A 1986; 83(21): 8064–8PubMedCrossRef

Nelson DR, Koymans L, Kamataki T, et al. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics 1996; 6(1): 1–42PubMedCrossRef

Wrighton SA, Ring BJ, Watkins PB, et al. Identification of a polymorphically expressed member of the human cytochrome P-450III family. Mol Pharmacol 1989; 36(1): 97–105PubMed

Aoyama T, Yamano S, Waxman DJ, et al. Cytochrome P450 hPCN3, a novel cytochrome P450 IIA gene product that is differentially expressed in adult human liver. J Biol Chem 1989; 264: 10388–95PubMed

Schuetz JD, Molowa DT, Guzelian PS. Characterization of a cDNA encoding a new member of the glucocorticoid-responsive cytochromes P450 in human liver. Arch Biochem Biophys 1989; 274(2): 355–65PubMedCrossRef

Kitada M, Kamataki T, Itahashi K, et al. P-450 HFLa, a form of cytochrome P-450 purified from human fetal livers, is the 16 alpha-hydroxylase of dehydroepiandrosterone 3-sulfate. J Biol Chem 1987; 262(28): 13534–7PubMed

10.

Wrighton SA, Vandenbranden M. Isolation and characterization of human fetal liver cytochrome P450HLp2: a third member of the P450III gene family. Arch Biochem Biophys 1989; 268(1): 144–51PubMedCrossRef

11.

Komori M, Nishio K, Fujitani T, et al. Isolation of a new human fetal liver cytochrome P450 cDNA clone: evidence for expression of a limited number of forms of cytochrome P450 in human fetal livers. Arch Biochem Biophys 1989; 272(1): 219–25PubMedCrossRef

12.

Domanski TL, Finta C, Halpert JR, et al. cDNA cloning and initial characterization of CYP3A43, a novel human cytochrome P450. Mol Pharmacol 2001; 59(2): 386–92PubMed

13.

Gellner K, Eiselt R, Hustert E, et al. Genomic organization of the human CYP3A locus: identification of a new, inducible CYP3A gene. Pharmacogenetics 2001; 11(2): 111–21PubMedCrossRef

14.

Westlind A, Malmebo S, Johansson I, et al. Cloning and tissue distribution of a novel human cytochrome P450 of the CYP3A subfamily, CYP3A43. Biochem Biophys Res Commun 2001; 281(5): 1349–55PubMedCrossRef

15.

Guengerich FP. Cytochrome P450 3A4: regulation and role in drug metabolism. Annu Rev Pharmacol Toxicol 1999; 39: 1–17PubMedCrossRef

16.

Wrighton SA, Brian WR, Sari MA, et al. Studies on the expression and metabolic capabilities of human liver cytochrome P450iiia5 (Hlp3). Mol Pharmacol 1990; 38: 207–13PubMed

17.

Jounaidi Y, Hyrailles V, Gervot L, et al. Detection of CYP3A5 allelic variant: a candidate for the polymorphic expression of the protein?. Biochem Biophys Res Commun 1996; 221(2): 466–70PubMedCrossRef

18.

Hustert E, Haberl M, Burk O, et al. The genetic determinants of the CYP3A5 polymorphism. Pharmacogenetics 2001; 11(9): 773–9PubMedCrossRef

19.

Paulussen A, Lavirijsen K, Bohets H, et al. Two linked mutations in transcriptional regulatory elements of the CYP3A5 gene constitute the major genetic determinant of polymorphic activity in humans. Pharmacogenetics 2000; 10: 415–24PubMedCrossRef

20.

Finta C, Zaphiropoulos PG. The human cytochrome P450 3A locus: gene evolution by capture of downstream exons. Gene 2000; 260(1–2): 13–23PubMedCrossRef

21.

Kuehl P, Zhang J, Lin Y, et al. Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression. Nature Genet 2001; 27(4): 383–91PubMedCrossRef

22.

Chou FC, Tzeng SJ, Huang JD. Genetic polymorphism of cytochrome P450 3A5 in Chinese. Drug Metab Dispos 2001; 29(9): 1205–9PubMed

23.

Lee SJ, Usmani KA, Chanas B, et al. Genetic findings and functional studies of human CYP3A5 single nucleotide polymorphisms in different ethnic groups. Pharmacogenetics 2003; 13(8): 461–72PubMedCrossRef

24.

Saeki M, Saito Y, Nakamura T, et al. Single nucleotide polymorphisms and haplotype frequencies of CYP3A5 in a Japanese population. Hum Mutat 2003; 21(6): 653PubMedCrossRef

25.

Westlind A, Lofberg L, Tindberg N, et al. Interindividual differences in hepatic expression of CYP3A4: relationship to genetic polymorphism in the 5′-upstream regulatory region. Biochem Biophys Res Commun 1999; 259(1): 201–5PubMedCrossRef

26.

Fukushima-Uesaka H, Saito Y, Watanabe H, et al. Haplotypes of CYP3A4 and their close linkage with CYP3A5 haplotypes in a Japanese population. Hum Mutat 2004; 23(1): 100PubMedCrossRef

27.

Xie HG, Wood AJ, Kim RB, et al. Genetic variability in CYP3A5 and its possible consequences. Pharmacogenomics 2004; 5(3): 243–72PubMedCrossRef

28.

Van Schaik RHN, Van Der Heiden IP, Van Den Anker JN, et al. CYP3A5 variant allele frequencies in Dutch Caucasians. Clin Chem 2002; 48(10): 1668–71PubMed

29.

King BP, Leathart JB, Mutch E, et al. CYP3A5 phenotypegenotype correlations in a British population. Br J Clin Pharmacol 2003; 55(6): 625–9PubMedCrossRef

30.

Dally H, Edler L, Jager B, et al. The CYP3A4*1B allele increases risk for small cell lung cancer: effect of gender and smoking dose. Pharmacogenetics 2003; 13(10): 607–18PubMedCrossRef

31.

Balram C, Zhou QY, Cheung YB, et al. CYP3A5*3 and *6 single nucleotide polymorphisms in three distinct Asian populations. Eur J Clin Pharmacol 2003; 59(2): 123–6PubMed

32.

Hiratsuka M, Takekuma Y, Endo N, et al. Allele and genotype frequencies of CYP2B6 and CYP3A5 in the Japanese population. Eur J Clin Pharmacol 2002; 58(6): 417–21PubMedCrossRef

33.

Fukuen S, Fukuda T, Maune H, et al. Novel detection assay by PCR-RFLP and frequency of the CYP3A5 SNPs, CYP3A5*3 and *6, in a Japanese population. Pharmacogenetics 2002; 12(4): 331–4PubMedCrossRef

34.

Lin YS, Dowling ALS, Quigley SD, et al. Co-regulation of CYP3A4 and CYP3A5 and contribution to hepatic and intestinal midazolam metabolism. Mol Pharmacol 2002; 62(1): 162–72PubMedCrossRef

35.

Westlind-Johnsson A, Malmebo S, Johansson A, et al. Comparative analysis of CYP3A expression in human liver suggests only a minor role for CYP3A5 in drug metabolism. Drug Metab Dispos 2003; 31(6): 755–61PubMedCrossRef

36.

Yamaori S, Yamazaki H, Iwano S, et al. CYP3A5 contributes significantly to CYP3A-mediated drug oxidations in liver microsomes from Japanese subjects. Drug Metab Pharmacokinet 2004; 19(2): 120–9PubMedCrossRef

37.

Koch I, Weil R, Wolbold R, et al. Interindividual variability and tissue-specificity in the expression of cytochrome P450 3A mRNA. Drug Metab Dispos 2002; 30(10): 1108–14PubMedCrossRef

38.

Williams JA, Cook J, Hurst SI. Significant drug-metabolizing role for CYP3A5?. Drug Metab Dispos 2003; 31(12): 1526–31PubMedCrossRef

39.

Paine MF, Khalighi M, Fisher JM, et al. Characterization of interintestinal and intraintestinal variations in human CYP3A-dependent metabolism. J Pharmacol Exp Ther 1997; 283(3): 1552–62PubMed

40.

Gervot L, Carriere V, Costet P, et al. CYP3A5 is the major cytochrome P450 3A expressed in human colon and colonic cell lines. Environ Toxicol Pharmacol 1996; 2(4): 381–8PubMedCrossRef

41.

Haehner BD, Gorski JC, Vandenbranden M, et al. Bimodal distribution of renal cytochrome P450 3A activity in humans. Mol Pharmacol 1996; 50(1): 52–9PubMed

42.

Kivisto KT, Fritz P, Linder A, et al. Immunohistochemical localization of cytochrome-P450 3A in human pulmonary carcinomas and normal bronchial tissue. Histochem Cell Biol 1995; 103(1): 25–9PubMedCrossRef

43.

Lechevrel M, Casson AG, Wolf CR, et al. Characterization of cytochrome P450 expression in human oesophageal mucosa. Carcinogenesis 1999; 20(2): 243–8PubMedCrossRef

44.

Murray GI, Pritchard S, Melvin WT, et al. Cytochrome-P450 CYP3A5 in the human anterior-pituitary gland. FEBS Lett 1995; 364(1): 79–82PubMedCrossRef

45.

Gibson GG, Plant NJ, Swales KE, et al. Receptor-dependent transcriptional activation of cytochrome P4503A genes: induction mechanisms, species differences and interindividual variation in man. Xenobiotica 2002; 32(3): 165–206PubMedCrossRef

46.

Jounaidi Y, Guzelian PS, Maurel P, et al. Sequence of the 5′-flanking region of CYP3A5: comparative analysis with CYP3A4 and CYP3A7. Biochem Biophys Res Commun 1994; 205(3): 1741–7PubMedCrossRef

47.

Schuetz JD, Schuetz EG, Thottassery JV, et al. Identification of a novel dexamethasone responsive enhancer in the human CYP3A5 gene and its activation in human and rat liver cells. Mol Pharmacol 1996; 49(1): 63–72PubMed

48.

Iwano S, Saito T, Takahashi Y, et al. Cooperative regulation of CYP3A5 gene transcription by NF-Y and Sp family members. Biochem Biophys Res Commun 2001; 286(1): 55–60PubMedCrossRef

49.

Hukkanen J, Vaisanen T, Lassila A, et al. Regulation of CYP3A5 by glucocorticoids and cigarette smoke in human lung-derived cells. J Pharmacol Exp Ther 2003; 304(2): 745–52PubMedCrossRef

50.

Rodriguez-Antona C, Jover R, Gomez-Lechon MJ, et al. Quantitative RT-PCR measurement of human cytochrome P-450s: application to drug induction studies. Arch Biochem Biophys 2000; 376(1): 109–16PubMedCrossRef

51.

Asghar A, Gorski JC, Haehner-Daniels B, et al. Induction of multidrug resistance-1 and cytochrome P450 mRNAs in human mononuclear cells by rifampin. Drug Metab Dispos 2002; 30(1): 20–6PubMedCrossRef

52.

Burk O, Koch I, Raucy J, et al. The induction of cytochrome P450 3A5 (CYP3A5) in the human liver and intestine is mediated by the xenobiotic sensors pregnane X receptor (PXR) and constitutively activated receptor (CAR). J Biol Chem 2004; 279(37): 38379–85PubMedCrossRef

53.

Schmiedlin-Ren P, Thummel KE, Fisher JM, et al. Expression of enzymatically active CYP3A4 by Caco-2 cells grown on extracellular matrix-coated permeable supports in the presence of 1α,25-dihydroxyvitamin D3. Mol Pharmacol 1997; 51(5): 741–54PubMed

54.

Crespi CL, Miller VP. The R144C change in the CYP2C9*2 allele alters interaction of the cytochrome P450 with NADPH: cytochrome P450 oxidoreductase. Pharmacogenetics 1997; 7(3): 203–10PubMedCrossRef

55.

Huang W, Lin YS, McConn II DJ, et al. Evidence of significant contribution from CYP3A5 to hepatic drug metabolism. Drug Metab Dispos 2004; 32(12): 1434–45PubMedCrossRef

56.

Patki KC, von Moltke LL, Greenblatt DJ. In vitro metabolism of midazolam, triazolam, nifedipine, and testosterone by human liver microsomes and recombinant cytochromes P450: role of CYP3A4 and CYP3A5. Drug Metab Dispos 2003; 31(7): 938–44PubMedCrossRef

57.

Williams JA, Ring BJ, Cantrell VE, et al. Comparative metabolic capabilities of CYP3A4, CYP3A5 and CYP3A7. Drug Metab Dispos 2002; 30: 883–91PubMedCrossRef

58.

Yamaori S, Yamazaki H, Suzuki A, et al. Effects of cytochrome b (5) on drug oxidation activities of human cytochrome P450 (CYP) 3As: similarity of CYP3A5 with CYP3A4 but not CYP3A7. Biochem Pharmacol 2003; 66(12): 2333–40PubMedCrossRef

59.

Galetin A, Brown C, Hallifax D, et al. Utility of recombinant enzyme kinetics in prediction of human clearance: impact of variability, CYP3A5, and CYP2C19 on CYP3A4 probe substrates. Drug Metab Dispos 2004; 32(12): 1411–20PubMedCrossRef

60.

Gorski JC, Hall SD, Jones DR, et al. Regioselective biotransformation of midazolam by members of the human cytochrome P450 3A (CYP3A) subfamily. Biochem Pharmacol 1994; 47(9): 1643–53PubMedCrossRef

61.

Gillam EM, Wunsch RM, Ueng YF, et al. Expression of cytochrome P450 3A7 in Escherichia coli: effects of 5′ modification and catalytic characterization of recombinant enzyme expressed in bicistronic format with NADPH-cytochrome P450 reductase. Arch Biochem Biophys 1997; 346(1): 81–90PubMedCrossRef

62.

Floyd MD, Gervasini G, Masica AL, et al. Genotype-phenotype associations for common CYP3A4 and CYP3A5 variants in the basal and induced metabolism of midazolam in European- and African-American men and women. Pharmacogenetics 2003; 13(10): 595–606PubMedCrossRef

63.

Eap CB, Buclin T, Hustert E, et al. Pharmacokinetics of midazolam in CYP3A4- and CYP3A5-genotyped subjects. Eur J Clin Pharmacol 2004; 60(4): 231–6PubMed

64.

Shih PS, Huang JD. Pharmacokinetics of midazolam and 1′-hydroxymidazolam in Chinese with different CYP3A5 genotypes. Drug Metab Dispos 2002; 30(12): 1491–6PubMedCrossRef

65.

Wong M, Balleine RL, Collins M, et al. CYP3A5 genotype and midazolam clearance in Australian patients receiving chemotherapy. Clin Pharmacol Ther 2004; 75(6): 529–38PubMedCrossRef

66.

Goh BC, Lee SC, Wang LZ, et al. Explaining interindividual variability of docetaxel pharmacokinetics and pharmacodynamics in Asians through phenotyping and genotyping strategies. J Clin Oncol 2002; 20(17): 3683–90PubMedCrossRef

67.

Macphee IAM, Fredericks S, Tai T, et al. Tacrolimus pharmacogenetics: polymorphisms associated with expression of cytochrome P4503A5 and P-glycoprotein correlate with dose requirement. Transplantation 2002; 74(11): 1486–9PubMedCrossRef

68.

Zheng HX, Webber S, Zeevi A, et al. Tacrolimus dosing in pediatric heart transplant patients is related to CYP3A5 and MDR1 gene polymorphisms. Am J Transplant 2003; 3(4): 477–83PubMedCrossRef

69.

Thervet E, Anglicheau D, King B, et al. Impact of cytochrome P450 3A5 genetic polymorphism on tacrolimus doses and concentration-to-dose ratio in renal transplant recipients. Transplantation 2003; 76(8): 1233–5PubMedCrossRef

70.

Hesselink DA, van Schaik RHN, van der Heiden IP, et al. Genetic polymorphisms of the CYP3A4, CYP3A5, and MDR-1 genes and pharmacokinetics of the calcineurin inhibitors cyclosporine and tacrolimus. Clin Pharmacol Ther 2003; 74(3): 245–54PubMedCrossRef

71.

Zheng HX, Zeevi A, Schuetz E, et al. Tacrolimus dosing in adult lung transplant patients is related to cytochrome P4503A5 gene polymorphism. J Clin Pharmacol 2004; 44(2): 135–40PubMedCrossRef

72.

Haufroid V, Mourad M, Van Kerckhove V, et al. The effect of CYP3A5 and MDR1 (ABCB1) polymorphisms on cyclosporine and tacrolimus dose requirements and trough blood levels in stable renal transplant patients. Pharmacogenetics 2004; 14(3): 147–54PubMedCrossRef

73.

Goto M, Masuda S, Kiuchi T, et al. CYP3A5*l-carrying graft liver reduces the concentration/oral dose ratio of tacrolimus in recipients of living-donor liver transplantation. Pharmacogenetics 2004; 14(7): 471–8PubMedCrossRef

74.

Tsuchiya N, Satoh S, Tada H, et al. Influence of CYP3A5 and MDR1 (ABCB1) polymorphisms on the pharmacokinetics of tacrolimus in renal transplant recipients. Transplantation 2004; 78(8): 1182–7PubMedCrossRef

75.

Yates CR, Zhang WH, Song PF, et al. The effect of CYP3A5 and MDR1 polymorphic expression on cyclosporine oral disposition in renal transplant patients. J Clin Pharmacol 2003; 43(6): 555–64PubMed

76.

Anglicheau D, Thervet E, Etienne I, et al. CYP3A5 and MDR1 genetic polymorphisms and cyclosporine pharmacokinetics after renal transplantation. Clin Pharmacol Ther 2004; 75(5): 422–33PubMedCrossRef

77.

Kreutz R, Zurcher H, Kain S, et al. The effect of variable CYP3A5 expression on cyclosporine dosing, blood pressure and long-term graft survival in renal transplant patients. Pharmacogenetics 2004; 14(10): 665–71PubMedCrossRef

78.

Bader A, Hansen T, Kirchner G, et al. Primary porcine enterocyte and hepatocyte cultures to study drug oxidation reactions. Br J Pharmacol 2000; 129(2): 331–42PubMedCrossRef

79.

Fukuda T, Onishi S, Fukuen S, et al. CYP3A5 genotype did not impact on nifedipine disposition in healthy volunteers. Pharmacogenomics J 2004; 4(1): 34–9PubMedCrossRef

80.

Shou M, Martinet M, Korzekwa KR, et al. Role of human cytochrome P450 3A4 and 3A5 in the metabolism of taxotere and its derivatives: enzyme specificity, interindividual distribution and metabolic contribution in human liver. Pharmacogenetics 1998; 8(5): 391–401PubMedCrossRef

81.

Katz DA, Grimm DR, Cassar SC, et al. CYP3A5 genotype has a dose-dependent effect on ABT-773 plasma levels. Clin Pharmacol Ther 2004; 75(6): 516–28PubMedCrossRef

82.

Gibbs MA, Thummel KE, Shen DD, et al. Inhibition of cytochrome P-450 3A (CYP3A) in human intestinal and liver microsomes: comparison of K_i values and impact of CYP3A5 expression. Drug Metab Dispos 1999; 27(2): 180–7PubMed

83.

Jones DR, Gorski JC, Hamman MA, et al. Diltiazem inhibition of cytochrome P-450 3A activity is due to metabolite intermediate complex formation. J Pharmacol Exp Ther 1999; 290(3): 1116–25PubMed

84.

Khan KK, He YQ, Correia MA, et al. Differential oxidation of mifepristone by cytochromes P450 3A4 and 3A5: selective inactivation of P450 3A4. Drug Metab Dispos 2002; 30(9): 985–90PubMedCrossRef

85.

McConn II DJ, Lin YS, Allen K, et al. Differences in the inhibition of cytochromes P450 3A4 and 3A5 by metabolite-inhibitor complex-forming drugs. Drug Metab Dispos 2004; 32(10): 1083–91PubMed

86.

Rebbeck TR, Jaffe JM, Walker AH, et al. Modification of clinical presentation of prostate tumors by a novel genetic variant in CYP3A4. J Natl Cancer Inst 1998; 90(16): 1225–9PubMedCrossRef

87.

Paris PL, Kupelian PA, Hall JM, et al. Association between a CYP3A4 genetic variant and clinical presentation in African-American prostate cancer patients. Cancer Epidemiol Biomarkers Prev 1999; 8(10): 901–5PubMed

88.

Plummer SJ, Conti DV, Paris PL, et al. CYP3A4 and CYP3A5 genotypes, haplotypes, and risk of prostate cancer. Cancer Epidemiol Biomarkers Prev 2003; 12(9): 928–32PubMed

89.

Modugno F, Knoll C, Kanbour-Shakir A, et al. A potential role for the estrogen-metabolizing cytochrome P450 enzymes in human breast carcinogenesis. Breast Cancer Res Treat 2003; 82(3): 191–7PubMedCrossRef

90.

Spurdle AB, Goodwin B, Hodgson E, et al. The CYP3A4*1B polymorphism has no functional significance and is not associated with risk of breast or ovarian cancer. Pharmacogenetics 2002; 12(5): 355–66PubMedCrossRef

91.

Kadlubar FF, Berkowitz GS, Delongchamp RR, et al. The CYP3A4*1B variant is related to the onset of puberty, a known risk factor for the development of breast cancer. Cancer Epidemiol Biomarkers Prev 2003; 12(4): 327–31PubMed

92.

Liu TC, Lin SF, Chen TP, et al. Polymorphism analysis of CYP3A5 in myeloid leukemia. Oncol Rep 2002; 9(2): 327–9PubMed

93.

Blanco JG, Edick MJ, Hancock ML, et al. Genetic polymorphisms in CYP3A5, CYP3A4 and NQO1 in children who developed therapy-related myeloid malignancies. Pharmacogenetics 2002; 12(8): 605–11PubMedCrossRef

94.

Felix CA, Walker AH, Lange BJ, et al. Association of CYP3A4 genotype with treatment-related leukemia. Proc Natl Acad Sci U S A 1998; 95(22): 13176–81PubMedCrossRef

95.

Aplenc R, Glatfelter W, Han P, et al. CYP3A genotypes and treatment response in paediatric acute lymphoblastic leukaemia. Br J Haematol 2003; 122(2): 240–4PubMedCrossRef

96.

Givens RC, Lin YS, Dowling ALS, et al. CYP3A5 genotype predicts renal CYP3A activity and blood pressure in healthy adults. J Appl Physiol 2003; 95(3): 1297–300PubMed

97.

Shimada T, Yamazaki H, Mimura M, et al. Characterization of microsomal cytochrome P450 enzymes involved in the oxidation of xenobiotic chemicals in human fetal liver and adult lungs. Drug Metab Dispos 1996; 24(5): 515–22PubMed

98.

Greuet J, Pichard L, Bonfils C, et al. The fetal specific gene CYP3A7 is inducible by rifampicin in adult human hepatocytes in primary culture. Biochem Biophys Res Commun 1996; 225(2): 689–94PubMedCrossRef

99.

Schuetz JD, Beach DL, Guzelian PS. Selective expression of cytochrome P450 CYP3A mRNAs in embryonic and adult human liver. Pharmacogenetics 1994; 4(1): 11–20PubMedCrossRef

100.

Burk O, Tegu de H, Koch I, et al. Molecular mechanisms of polymorphic CYP3A7 expression in adult human liver and intestine. J Biol Chem 2002; 277(27): 24280–8PubMedCrossRef

101.

Stevens JC, Hines RN, Gu CG, et al. Developmental expression of the major human hepatic CYP3A enzymes. J Pharmacol Exp Ther 2003; 307(2): 573–82PubMedCrossRef

102.

Schuetz JD, Kauma S, Guzelian PS. Identification of the fetal liver cytochrome CYP3A7 in human endometrium and placenta. J Clin Invest 1993; 92(2): 1018–24PubMedCrossRef

103.

Sarkar MA, Vadlamuri V, Ghosh S, et al. Expression and cyclic variability of CYP3A4 and CYP3A7 isoforms in human endometrium and cervix during the menstrual cycle. Drug Metab Dispos 2003; 31(1): 1–6PubMedCrossRef

104.

Chen H, Fantel AG, Juchau MR. Catalysis of the 4-hydroxylation of retinoic acids by CYP3A7 in human fetal hepatic tissues. Drug Metab Dispos 2000; 28(9): 1051–7PubMed

105.

Marill J, Cresteil T, Lanotte M, et al. Identification of human cytochrome P450s involved in the formation of all-trans-retinoic acid principal metabolites. Mol Pharmacol 2000; 58(6): 1341–8PubMed

106.

Clagett-Dame M, DeLuca HF. The role of vitamin A in mammalian reproduction and embryonic development. Annu Rev Nutr 2002; 22: 347–81PubMedCrossRef

107.

Lee AJ, Conney AH, Zhu BT. Human cytochrome P450 3A7 has a distinct high catalytic activity for the 16α-hydroxylation of estrone but not 17β-estradiol. Cancer Res 2003; 63(19): 6532–6PubMed

108.

Pascussi JM, Jounaidi Y, Drocourt L, et al. Evidence for the presence of a functional pregnane X receptor response element in the CYP3A7 promoter gene. Biochem Biophys Res Commun 1999; 260(2): 377–81PubMedCrossRef

109.

Bertilsson G, Berkenstam A, Blomquist P. Functionally conserved xenobiotic responsive enhancer in cytochrome P450 3A7. Biochem Biophys Res Commun 2001; 280(1): 139–44PubMedCrossRef

110.

Matsunaga T, Maruyama M, Harada E, et al. Expression and induction of CYP3As in human fetal hepatocytes. Biochem Biophys Res Commun 2004; 318(2): 428–34PubMedCrossRef

111.

Hashimoto H, Toide K, Kitamura R, et al. Gene structure of CYP3A4, an adult-specific form of cytochrome P450 in human livers, and its transcriptional control. Eur J Biochem 1993; 218(2): 585–95PubMedCrossRef

112.

Krusekopf S, Roots I, Kleeberg U. Differential drug-induced mRNA expression of human CYP3A4 compared to CYP3A5, CYP3A7 and CYP3A43. Eur J Pharmacol 2003; 466(1–2): 7–12PubMedCrossRef

113.

Cauffiez C, Lo-Guidice JM, Chevalier D, et al. First report of a genetic polymorphism of the cytochrome P450 3A43 (CYP3A43) gene: identification of a loss-of-function variant. Hum Mutat 2004; 23(1): 101PubMedCrossRef

114.

Zeigler-Johnson C, Friebel T, Walker AH, et al. CYP3A4, CYP3A5, and CYP3A43 genotypes and haplotypes in the etiology and severity of prostate cancer. Cancer Res 2004; 64(22): 8461–7PubMedCrossRef

115.

Stone A, Ratnasinghe LD, Emerson GL, et al. CYP3A43 Pro(340) Ala polymorphism and prostate cancer risk in African Americans and Caucasians. Cancer Epidemiol Biomarkers Prev. 2005 May; 14(5): 1257–61PubMedCrossRef

116.

Kamdem LK, Streit F, Zanger UM, et al. Contribution of CYP3A5 to the in vitro hepatic clearance of tacrolimus. Clin Chem 2005 Aug; 51(8): 1374–81PubMedCrossRef

117.

Fromm MF, Schmidt BM, Pahl A, et al. CYP3A5 genotype is associated with elevated blood pressure. Pharmacogenet Genomics 2005 Oct; 15(10): 737–41PubMedCrossRef

118.

Ho H, Pinto A, Hall SD, et al. Association between the CYP3A5 genotype and blood pressure. Hypertension 2005 Feb; 45(2): 294–8PubMedCrossRef

119.

Rivisto KT, Niemi M, Schaeffeler E, et al. CYP3A5 genotype is associated with diagnosis of hypertension in elderly patients: data from the DEBATE Study. Am J Pharmacogenomics 2005; 5(3): 191–5CrossRef

120.

Kreutz R, Zuurman M, Kain S, et al. The role of the cytochrome P450 3A5 enzyme for blood pressure regulation in the general Caucasian population. Pharmacogenet Genomics 2005 Dec; 15(12): 831–7PubMedCrossRef

121.

Sim SC, Edwards RJ, Boobis AR, et al. CYP3A7 protein expression is high in a fraction of adult human livers and partially associated with the CYP3A7*1C allele. Pharmacogenet Genomics 2005 Sep; 15(9): 625–31PubMedCrossRef

Title: Significance of the Minor Cytochrome P450 3A Isoforms
Author: Dr Ann K. Daly
Publication date: 01-01-2006
Publisher: Springer International Publishing
Published in: Clinical Pharmacokinetics / Issue 1/2006
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI: https://doi.org/10.2165/00003088-200645010-00002

At a glance: The STEP trials

Springer Medicine

Significance of the Minor Cytochrome P450 3A Isoforms

Abstract

At a glance: The STEP trials

Springer Medicine

Abstract

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