Pharmacogenetic considerations for optimizing tacrolimus dosing in liver and kidney transplant patients

World Journal of Gastroenterology

Volumn 19, Issue 48, 2013, Pages 9156-9173

  Provenzani, Alessio ^a   Santeusanio, Andrew ^b   Mathis, Erin ^b   Notarbartolo, Monica ^c   Labbozzetta, Manuela ^c   Poma, Paola ^c   Provenzani, Ambra ^d   Polidori, Carlo ^e   Vizzini, Giovanni ^a   Polidori, Piera ^a   D'Alessandro, Natale ^c  

^a MEDITERRANEAN INSTITUTE FOR TRANSPLANTATION AND ADVANCED SPECIALIZED THERAPIES ISMETT   (Italy)

^b UNIVERSITY OF PITTSBURGH   (United States)

^c UNIVERSITY OF PALERMO   (Italy)

^d National Institute of Social Security (INPS)   (Italy)

^e UNIVERSITY OF CAMERINO   (Italy)

Author keywords

ABCB1; Calcineurin inhibitors; CYP3A4; CYP3A5; Kidney transplant; Liver transplant; Pharmacogenetics; Single nucleotide polymorphisms; Tacrolimus

Indexed keywords

ALBUMIN; ANGIOTENSINOGEN; CORTICOSTEROID; CYCLOSPORIN; CYTOCHROME P450 2C8; CYTOCHROME P450 2J2; CYTOCHROME P450 3A4; CYTOCHROME P450 3A5; CYTOCHROME P450 3A7; CYTOCHROME P450 REDUCTASE; DILTIAZEM; INTERLEUKIN 2; MULTIDRUG RESISTANCE PROTEIN 1; TACROLIMUS; TRANSCRIPTION FACTOR 7;

ALLELE; ARTICLE; DRUG EFFICACY; DRUG SAFETY; GENETIC ASSOCIATION; GENETIC LINKAGE; GENETIC POLYMORPHISM; GENOTYPE; GRAFT SURVIVAL; HEMATOCRIT; HEREDITY; HUMAN; HYPERESTHESIA; HYPERGLYCEMIA; HYPERLIPIDEMIA; HYPERTENSION; INSOMNIA; KIDNEY TRANSPLANTATION; LIVER TRANSPLANTATION; NEPHROTOXICITY; PHARMACOGENETICS; PROTEIN EXPRESSION; SEIZURE; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; TREMOR;

ABCB1; CALCINEURIN INHIBITORS; CYP3A4; CYP3A5; KIDNEY TRANSPLANT; LIVER TRANSPLANT; PHARMACOGENETICS; SINGLE NUCLEOTIDE POLYMORPHISMS; TACROLIMUS;

BIOTRANSFORMATION; CYTOCHROME P-450 CYP3A; DRUG DOSAGE CALCULATIONS; GENOTYPE; GRAFT REJECTION; GRAFT SURVIVAL; HUMANS; IMMUNOSUPPRESSIVE AGENTS; KIDNEY TRANSPLANTATION; LIVER TRANSPLANTATION; P-GLYCOPROTEIN; PHARMACOGENETICS; PHENOTYPE; POLYMORPHISM, GENETIC; TACROLIMUS; TREATMENT OUTCOME;

EID: 84891474968     PISSN: 10079327     EISSN: 22192840     Source Type: Journal    
DOI: 10.3748/wjg.v19.i48.9156     Document Type: Article

References (128)

1. Murray JE, Tilney NL, Wilson RE. Renal transplantation: a twenty-five year experience. Ann Surg 1976; 184: 565-573 [PMID: 791162]
2. Penninga L, Wettergren A, Chan AW, Steinbrüchel DA, Gluud C. Calcineurin inhibitor minimisation versus continuation of calcineurin inhibitor treatment for liver transplant recipients. Cochrane Database Syst Rev 2012; 3: CD008852 [PMID: 22419339 DOI: 10.1002/14651858.CD008852]
3. Ponticelli C. Present and future of immunosuppressive therapy in kidney transplantation. Transplant Proc 2011; 43: 2439-2440 [PMID: 21839286 DOI: 10.1016/j.transproceed.2011.06.025]
4. Venkataramanan R, Swaminathan A, Prasad T, Jain A, Zuckerman S, Warty V, McMichael J, Lever J, Burckart G, Starzl T. Clinical pharmacokinetics of tacrolimus. Clin Pharmacokinet 1995; 29: 404-430 [PMID: 8787947]
5. Undre NA, Stevenson P, Schäfer A. Pharmacokinetics of tacrolimus: clinically relevant aspects. Transplant Proc 1999; 31: 21S-24S [PMID: 10576037]
6. Budde K, Glander P. Pharmacokinetic principles of immunosuppressive drugs. Ann Transplant 2008; 13: 5-10 [PMID: 18806727]
7. Schiff J, Cole E, Cantarovich M. Therapeutic monitoring of calcineurin inhibitors for the nephrologist. Clin J Am Soc Nephrol 2007; 2: 374-384 [PMID: 17699437]
8. Mohammadpour N, Elyasi S, Vahdati N, Mohammadpour AH, Shamsara J. A review on therapeutic drug monitoring of immunosuppressant drugs. Iran J Basic Med Sci 2011; 14: 485-498 [PMID: 23493821]
9. Danesi R, Mosca M, Boggi U, Mosca F, Del Tacca M. Genetics of drug response to immunosuppressive treatment and prospects for personalized therapy. Mol Med Today 2000; 6: 475-482 [PMID: 11099953]
10. Johnston A, Holt DW. Immunosuppressant drugs--the role of therapeutic drug monitoring. Br J Clin Pharmacol 2001; 52 Suppl 1: 61S-73S [PMID: 11564054]
11. Yagil Y, Yagil C. Insights into pharmacogenomics and its impact upon immunosuppressive therapy. Transpl Immunol 2002; 9: 203-209 [PMID: 12180832]
12. Cattaneo D, Perico N, Remuzzi G. From pharmacokinetics to pharmacogenomics: a new approach to tailor immunosuppressive therapy. Am J Transplant 2004; 4: 299-310 [PMID: 14961981]
13. Kalow W. The Pennsylvania State University College of Medicine 1990 Bernard B. Brodie Lecture. Pharmacogenetics: past and future. Life Sci 1990; 47: 1385-1397 [PMID: 2250557]
14. McCarthy JJ, Hilfiker R. The use of single-nucleotide polymorphism maps in pharmacogenomics. Nat Biotechnol 2000; 18: 505-508 [PMID: 10802616]
15. McGraw J, Waller D. Cytochrome P450 variations in different ethnic populations. Expert Opin Drug Metab Toxicol 2012; 8: 371-382 [PMID: 22288606 DOI: 10.1517/17425255.2012.657626]
16. De Gregori M, Allegri M, De Gregori S, Garbin G, Tinelli C, Regazzi M, Govoni S, Ranzani GN. How and why to screen for CYP2D6 interindividual variability in patients under pharmacological treatments. Curr Drug Metab 2010; 11: 276-282 [PMID: 21171195]
17. Ingelman-Sundberg M, Sim SC. Intronic polymorphisms of cytochromes P450. Hum Genomics 2010; 4: 402-405 [PMID: 20846929]
18. Murray B, Hawes E, Lee RA, Watson R, Roederer MW. Genes and beans: pharmacogenomics of renal transplant. Pharmacogenomics 2013; 14: 783-798 [PMID: 23651025 DOI: 10.2217/ pgs.13.68]
19. Tanaka H, Kuroda A, Marusawa H, Hashimoto M, Hatanaka H, Kino T, Goto T, Okuhara M. Physicochemical properties of FK-506, a novel immunosuppressant isolated from Streptomyces tsukubaensis. Transplant Proc 1987; 19: 11-16 [PMID: 2445067]
20. Sawada S, Suzuki G, Kawase Y, Takaku F. Novel immunosuppressive agent, FK506. In vitro effects on the cloned T cell activation. J Immunol 1987; 139: 1797-1803 [PMID: 2442255]
21. Kelly PA, Burckart GJ, Venkataramanan R. Tacrolimus: a new immunosuppressive agent. Am J Health Syst Pharm 1995; 52: 1521-1535 [PMID: 7552894]
22. Morris R. Modes of action of FK506, cyclosporin A, and rapamycin. Transplant Proc 1994; 26: 3272-3275 [PMID: 7527964]
23. Thiebaut F, Tsuruo T, Hamada H, Gottesman MM, Pastan I, Willingham MC. Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc Natl Acad Sci USA 1987; 84: 7735-7738 [PMID: 2444983]
24. Anglicheau D, Verstuyft C, Laurent-Puig P, Becquemont L, Schlageter MH, Cassinat B, Beaune P, Legendre C, Thervet E. Association of the multidrug resistance-1 gene single-nucleotide polymorphisms with the tacrolimus dose requirements in renal transplant recipients. J Am Soc Nephrol 2003; 14: 1889-1896 [PMID: 12819250]
25. Hoffmeyer S, Burk O, von Richter O, Arnold HP, Brockmöller J, Johne A, Cascorbi I, Gerloff T, Roots I, Eichelbaum M, Brinkmann U. Functional polymorphisms of the human multidrugresistance gene: multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci USA 2000; 97: 3473-3478 [PMID: 10716719]
26. Li Y, Hu X, Cai B, Chen J, Bai Y, Tang J, Liao Y, Wang L. Metaanalysis of the effect of MDR1 C3435 polymorphism on tacrolimus pharmacokinetics in renal transplant recipients. Transpl Immunol 2012; 27: 12-18 [PMID: 22504573 DOI: 10.1016/ j.trim.2012.03.006]
27. Akbas SH, Bilgen T, Keser I, Tuncer M, Yucetin L, Tosun O, Gultekin M, Luleci G. The effect of MDR1 (ABCB1) polymorphism on the pharmacokinetic of tacrolimus in Turkish renal transplant recipients. Transplant Proc 2006; 38: 1290-1292 [PMID: 16797284]
28. Singh R, Srivastava A, Kapoor R, Mittal RD. Do drug transporter (ABCB1) SNPs influence cyclosporine and tacrolimus dose requirements and renal allograft outcome in the posttransplantation period? J Clin Pharmacol 2011; 51: 603-615 [PMID: 20571034 DOI: 10.1177/0091270010370704]
29. Tsuchiya N, Satoh S, Tada H, Li Z, Ohyama C, Sato K, Suzuki T, Habuchi T, Kato T. Influence of CYP3A5 and MDR1 (ABCB1) polymorphisms on the pharmacokinetics of tacrolimus in renal transplant recipients. Transplantation 2004; 78: 1182-1187 [PMID: 15502717]
30. Fredericks S, Moreton M, Reboux S, Carter ND, Goldberg L, Holt DW, MacPhee IA. Multidrug resistance gene-1 (MDR-1) haplotypes have a minor influence on tacrolimus dose requirements. Transplantation 2006; 82: 705-708 [PMID: 16969296]
31. von Ahsen N, Richter M, Grupp C, Ringe B, Oellerich M, Armstrong VW. No influence of the MDR-1 C3435T polymorphism or a CYP3A4 promoter polymorphism (CYP3A4-V allele) on dose-adjusted cyclosporin A trough concentrations or rejection incidence in stable renal transplant recipients. Clin Chem 2001; 47: 1048-1052 [PMID: 11375290]
32. Saeki T, Ueda K, Tanigawara Y, Hori R, Komano T. Human P-glycoprotein transports cyclosporin A and FK506. J Biol Chem 1993; 268: 6077-6080 [PMID: 7681059]
33. Gervasini G, Garcia M, Macias RM, Cubero JJ, Caravaca F, Benitez J. Impact of genetic polymorphisms on tacrolimus pharmacokinetics and the clinical outcome of renal transplantation. Transpl Int 2012; 25: 471-480 [PMID: 22369694 DOI:10.1111/j.1432-2277.2012.01446.x]
34. May DG, Porter J, Wilkinson GR, Branch RA. Frequency distribution of dapsone N-hydroxylase, a putative probe for P4503A4 activity, in a white population. Clin Pharmacol Ther 1994; 55: 492-500 [PMID: 8181193]
35. Machado CG, Calado RT, Garcia AB, Falcão RP. Age-related changes of the multidrug resistance P-glycoprotein function in normal human peripheral blood T lymphocytes. Braz J Med Biol Res 2003; 36: 1653-1657 [PMID: 14666249]
36. Ameyaw MM, Regateiro F, Li T, Liu X, Tariq M, Mobarek A, Thornton N, Folayan GO, Githang'a J, Indalo A, Ofori-Adjei D, Price-Evans DA, McLeod HL. MDR1 pharmacogenetics: frequency of the C3435T mutation in exon 26 is significantly influenced by ethnicity. Pharmacogenetics 2001; 11: 217-221 [PMID: 11337937]
37. Dirks NL, Huth B, Yates CR, Meibohm B. Pharmacokinetics of immunosuppressants: a perspective on ethnic differences. Int J Clin Pharmacol Ther 2004; 42: 701-718 [PMID: 15624287]
38. Uesugi M, Masuda S, Katsura T, Oike F, Takada Y, Inui K. Effect of intestinal CYP3A5 on postoperative tacrolimus trough levels in living-donor liver transplant recipients. Pharmacogenet Genomics 2006; 16: 119-127 [PMID: 16424824]
39. Undre N, Möller A. Pharmacokinetic interpretation of FK 506 levels in blood and in plasma during a European randomised study in primary liver transplant patients. The FK 506 European Study Group. Transpl Int 1994; 7 Suppl 1: S15-S21 [PMID: 11271189]
40. Hu RH, Lee PH, Tsai MK. Clinical influencing factors for daily dose, trough level, and relative clearance of tacrolimus in renal transplant recipients. Transplant Proc 2000; 32: 1689-1692 [PMID: 11119894]
41. Ihara H, Shinkuma D, Ichikawa Y, Nojima M, Nagano S, Ikoma F. Intra-and interindividual variation in the pharmaco-kinetics of tacrolimus (FK506) in kidney transplant recipients--importance of trough level as a practical indicator. Int J Urol 1995; 2: 151-155 [PMID: 8536129]
42. Jusko WJ. Analysis of tacrolimus (FK 506) in relation to therapeutic drug monitoring. Ther Drug Monit 1995; 17: 596-601 [PMID: 8588227]
43. Herrero MJ, Sánchez-Plumed J, Galiana M, Bea S, Marqués MR, Aliño SF. Influence of pharmacogenetic polymorphisms in routine immunosuppression therapy after renal transplantation. Transplant Proc 2010; 42: 3134-3136 [PMID: 20970628 DOI:10.1016/j.transproceed.2010.05.122]
44. Home page of the Human Cytochrome P450 (CYP) Allele Nomenclature Committee (online). Consulted 2013, June 03. Available from: URL: http://www.cypalleles.ki.se/
45. Rebbeck TR, Jaffe JM, Walker AH, Wein AJ, Malkowicz SB. Modification of clinical presentation of prostate tumors by a novel genetic variant in CYP3A4. J Natl Cancer Inst 1998; 90: 1225-1229 [PMID: 9719084]
46. Sata F, Sapone A, Elizondo G, Stocker P, Miller VP, Zheng W, Raunio H, Crespi CL, Gonzalez FJ. CYP3A4 allelic variants with amino acid substitutions in exons 7 and 12: evidence for an allelic variant with altered catalytic activity. Clin Pharmacol Ther 2000; 67: 48-56 [PMID: 10668853]
47. Ando Y, Tateishi T, Sekido Y, Yamamoto T, Satoh T, Hasegawa Y, Kobayashi S, Katsumata Y, Shimokata K, Saito H. Re: Modification of clinical presentation of prostate tumors by a novel genetic variant in CYP3A4. J Natl Cancer Inst 1999; 91: 1587-1590 [PMID: 10491442]
48. Westlind A, Löfberg L, Tindberg N, Andersson TB, Ingelman-Sundberg M. Interindividual differences in hepatic expression of CYP3A4: relationship to genetic polymorphism in the 5'-upstream regulatory region. Biochem Biophys Res Commun 1999; 259: 201-205 [PMID: 10334940]
49. Lamba JK, Lin YS, Thummel K, Daly A, Watkins PB, Strom S, Zhang J, Schuetz EG. Common allelic variants of cytochrome P4503A4 and their prevalence in different populations. Pharmacogenetics 2002; 12: 121-132 [PMID: 11875366]
50. Spurdle AB, Goodwin B, Hodgson E, Hopper JL, Chen X, Purdie DM, McCredie MR, Giles GG, Chenevix-Trench G, Liddle C. The CYP3A41B polymorphism has no functional significance and is not associated with risk of breast or ovarian cancer. Pharmacogenetics 2002; 12: 355-366 [PMID: 12142725]
51. Rodríguez-Antona C, Sayi JG, Gustafsson LL, Bertilsson L, Ingelman-Sundberg M. Phenotype-genotype variability in the human CYP3A locus as assessed by the probe drug quinine and analyses of variant CYP3A4 alleles. Biochem Biophys Res Commun 2005; 338: 299-305 [PMID: 16171783]
52. Amirimani B, Walker AH, Weber BL, Rebbeck TR. RESPONSE: re: modification of clinical presentation of prostate tumors by a novel genetic variant in CYP3A4 J Natl Cancer Inst 1999; 91: 1588-1590 [PMID: 10491443]
53. Amirimani B, Ning B, Deitz AC, Weber BL, Kadlubar FF, Rebbeck TR. Increased transcriptional activity of the CYP3A41B promoter variant. Environ Mol Mutagen 2003; 42: 299-305 [PMID: 14673875]
54. Ball SE, Scatina J, Kao J, Ferron GM, Fruncillo R, Mayer P, Weinryb I, Guida M, Hopkins PJ, Warner N, Hall J. Population distribution and effects on drug metabolism of a genetic variant in the 5' promoter region of CYP3A4. Clin Pharmacol Ther 1999; 66: 288-294 [PMID: 10511065]
55. García-Martín E, Martínez C, Pizarro RM, García-Gamito FJ, Gullsten H, Raunio H, Agúndez JA. CYP3A4 variant alleles in white individuals with low CYP3A4 enzyme activity. Clin Pharmacol Ther 2002; 71: 196-204 [PMID: 11907494]
56. Wandel C, Witte JS, Hall JM, Stein CM, Wood AJ, Wilkinson GR. CYP3A activity in African American and European American men: population differences and functional effect of the CYP3A41B5'-promoter region polymorphism. Clin Pharmacol Ther 2000; 68: 82-91 [PMID: 10945319]
57. Lamba JK, Lin YS, Schuetz EG, Thummel KE. Genetic contribution to variable human CYP3A-mediated metabolism. Adv Drug Deliv Rev 2002; 54: 1271-1294 [PMID: 12406645]
58. Lepper ER, Baker SD, Permenter M, Ries N, van Schaik RH, Schenk PW, Price DK, Ahn D, Smith NF, Cusatis G, Ingersoll RG, Bates SE, Mathijssen RH, Verweij J, Figg WD, Sparreboom A. Effect of common CYP3A4 and CYP3A5 variants on the pharmacokinetics of the cytochrome P450 3A phenotyping probe midazolam in cancer patients. Clin Cancer Res 2005; 11: 7398-7404 [PMID: 16243813]
59. Sinues B, Vicente J, Fanlo A, Vasquez P, Medina JC, Mayayo E, Conde B, Arenaz I, Martinez-Jarreta B. CYP3A53 and CYP3A41B allele distribution and genotype combinations: differences between Spaniards and Central Americans. Ther Drug Monit 2007; 29: 412-416 [PMID: 17667794]
60. Gervasini G, Vizcaino S, Gasiba C, Carrillo JA, Benitez J. Differences in CYP3A53 genotype distribution and combinations with other polymorphisms between Spaniards and Other Caucasian populations. Ther Drug Monit 2005; 27: 819-821 [PMID: 16306861]
61. Kuehl P, Zhang J, Lin Y, Lamba J, Assem M, Schuetz J, Watkins PB, Daly A, Wrighton SA, Hall SD, Maurel P, Relling M, Brimer C, Yasuda K, Venkataramanan R, Strom S, Thummel K, Boguski MS, Schuetz E. Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression. Nat Genet 2001; 27: 383-391 [PMID: 11279519]
62. Hustert E, Haberl M, Burk O, Wolbold R, He YQ, Klein K, Nuessler AC, Neuhaus P, Klattig J, Eiselt R, Koch I, Zibat A, Brockmöller J, Halpert JR, Zanger UM, Wojnowski L. The genetic determinants of the CYP3A5 polymorphism. Pharmacogenetics 2001; 11: 773-779 [PMID: 11740341]
63. Goto M, Masuda S, Kiuchi T, Ogura Y, Oike F, Okuda M, Tanaka K, Inui K. CYP3A51-carrying graft liver reduces the concentration/ oral dose ratio of tacrolimus in recipients of living-donor liver transplantation. Pharmacogenetics 2004; 14: 471-478 [PMID: 15226679]
64. Joy MS, Hogan SL, Thompson BD, Finn WF, Nickeleit V. Cytochrome P450 3A5 expression in the kidneys of patients with calcineurin inhibitor nephrotoxicity. Nephrol Dial Transplant 2007; 22: 1963-1968 [PMID: 17395652]
65. Zheng S, Tasnif Y, Hebert MF, Davis CL, Shitara Y, Calamia JC, Lin YS, Shen DD, Thummel KE. Measurement and compartmental modeling of the effect of CYP3A5 gene variation on systemic and intrarenal tacrolimus disposition. Clin Pharmacol Ther 2012; 92: 737-745 [PMID: 23073208 DOI: 10.1038/ clpt.2012.175]
66. Shi Y, Li Y, Tang J, Zhang J, Zou Y, Cai B, Wang L. Influence of CYP3A4, CYP3A5 and MDR-1 polymorphisms on tacrolimus pharmacokinetics and early renal dysfunction in liver transplant recipients. Gene 2013; 512: 226-231 [PMID: 23107770 DOI:10.1016/j.gene.2012.10.048]
67. Hesselink DA, van Schaik RH, van der Heiden IP, van der Werf M, Gregoor PJ, Lindemans J, Weimar W, van Gelder T. Genetic polymorphisms of the CYP3A4, CYP3A5, and MDR-1 genes and pharmacokinetics of the calcineurin inhibitors cyclosporine and tacrolimus. Clin Pharmacol Ther 2003; 74: 245-254 [PMID: 12966368]
68. Kuypers DR, de Jonge H, Naesens M, Lerut E, Verbeke K, Vanrenterghem Y. CYP3A5 and CYP3A4 but not MDR1 singlenucleotide polymorphisms determine long-term tacrolimus disposition and drug-related nephrotoxicity in renal recipients. Clin Pharmacol Ther 2007; 82: 711-725 [PMID: 17495880]
69. Hesselink DA, van Gelder T, van Schaik RH, Balk AH, van der Heiden IP, van Dam T, van der Werf M, Weimar W, Mathot RA. Population pharmacokinetics of cyclosporine in kidney and heart transplant recipients and the influence of ethnicity and genetic polymorphisms in the MDR-1, CYP3A4, and CYP3A5 genes. Clin Pharmacol Ther 2004; 76: 545-556 [PMID: 15592326]
70. Riordan JR, Deuchars K, Kartner N, Alon N, Trent J, Ling V. Amplification of P-glycoprotein genes in multidrug-resistant mammalian cell lines. Nature 1985; 316: 817-819 [PMID: 2863759]
71. Higgins CF, Callaghan R, Linton KJ, Rosenberg MF, Ford RC. Structure of the multidrug resistance P-glycoprotein. Semin Cancer Biol 1997; 8: 135-142 [PMID: 9441943]
72. Ganapathy V, Prasad PD, Ganapathy ME, Leibach FH. Placental transporters relevant to drug distribution across the maternal-fetal interface. J Pharmacol Exp Ther 2000; 294: 413-420 [PMID: 10900213]
73. Zhang Y, Benet LZ. The gut as a barrier to drug absorption: combined role of cytochrome P450 3A and P-glycoprotein. Clin Pharmacokinet 2001; 40: 159-168 [PMID: 11327196]
74. Fojo AT, Ueda K, Slamon DJ, Poplack DG, Gottesman MM, Pastan I. Expression of a multidrug-resistance gene in human tumors and tissues. Proc Natl Acad Sci USA 1987; 84: 265-269 [PMID: 2432605]
75. Tang K, Ngoi SM, Gwee PC, Chua JM, Lee EJ, Chong SS, Lee CG. Distinct haplotype profiles and strong linkage disequilibrium at the MDR1 multidrug transporter gene locus in three ethnic Asian populations. Pharmacogenetics 2002; 12: 437-450 [PMID: 12172212]
76. Anglicheau D, Thervet E, Etienne I, Hurault De Ligny B, Le Meur Y, Touchard G, Büchler M, Laurent-Puig P, Tregouet D, Beaune P, Daly A, Legendre C, Marquet P. CYP3A5 and MDR1 genetic polymorphisms and cyclosporine pharmacokinetics after renal transplantation. Clin Pharmacol Ther 2004; 75: 422-433 [PMID: 15116055]
77. Kroetz DL, Pauli-Magnus C, Hodges LM, Huang CC, Kawamoto M, Johns SJ, Stryke D, Ferrin TE, DeYoung J, Taylor T, Carlson EJ, Herskowitz I, Giacomini KM, Clark AG. Sequence diversity and haplotype structure in the human ABCB1 (MDR1, multidrug resistance transporter) gene. Pharmacogenetics 2003; 13: 481-494 [PMID: 12893986]
78. Woodahl EL, Hingorani SR, Wang J, Guthrie KA, McDonald GB, Batchelder A, Li M, Schoch HG, McCune JS. Pharmacogenomic associations in ABCB1 and CYP3A5 with acute kidney injury and chronic kidney disease after myeloablative hematopoietic cell transplantation. Pharmacogenomics J 2008; 8: 248-255 [PMID: 17700595]
79. Yamauchi A, Ieiri I, Kataoka Y, Tanabe M, Nishizaki T, Oishi R, Higuchi S, Otsubo K, Sugimachi K. Neurotoxicity induced by tacrolimus after liver transplantation: relation to genetic polymorphisms of the ABCB1 (MDR1) gene. Transplantation 2002; 74: 571-572 [PMID: 12352921]
80. Yanagimachi M, Naruto T, Tanoshima R, Kato H, Yokosuka T, Kajiwara R, Fujii H, Tanaka F, Goto H, Yagihashi T, Kosaki K, Yokota S. Influence of CYP3A5 and ABCB1 gene polymorphisms on calcineurin inhibitor-related neurotoxicity after hematopoietic stem cell transplantation. Clin Transplant 2010; 24: 855-861 [PMID: 20030680 DOI: 10.1111/j.1399-0012.2009.01181.x]
81. Wang D, Johnson AD, Papp AC, Kroetz DL, Sadée W. Multidrug resistance polypeptide 1 (MDR1, ABCB1) variant 3435C& gt; T affects mRNA stability. Pharmacogenet Genomics 2005; 15: 693-704 [PMID: 16141795]
82. Kimchi-Sarfaty C, Oh JM, Kim IW, Sauna ZE, Calcagno AM, Ambudkar SV, Gottesman MM. A "silent" polymorphism in the MDR1 gene changes substrate specificity. Science 2007; 315: 525-528 [PMID: 17185560]
83. Op den Buijsch RA, Christiaans MH, Stolk LM, de Vries JE, Cheung CY, Undre NA, van Hooff JP, van Dieijen-Visser MP, Bekers O. Tacrolimus pharmacokinetics and pharmacogenetics: influence of adenosine triphosphate-binding cassette B1 (ABCB1) and cytochrome (CYP) 3A polymorphisms. Fundam Clin Pharmacol 2007; 21: 427-435 [PMID: 17635182]
84. Cho JH, Yoon YD, Park JY, Song EJ, Choi JY, Yoon SH, Park SH, Kim YL, Kim CD. Impact of cytochrome P450 3A and ATPbinding cassette subfamily B member 1 polymorphisms on tacrolimus dose-adjusted trough concentrations among Korean renal transplant recipients. Transplant Proc 2012; 44: 109-114 [PMID: 22310591 DOI: 10.1016/j.transproceed.2011.11.004]
85. Roy JN, Barama A, Poirier C, Vinet B, Roger M. Cyp3A4, Cyp3A5, and MDR-1 genetic influences on tacrolimus pharmacokinetics in renal transplant recipients. Pharmacogenet Genomics 2006; 16: 659-665 [PMID: 16906020]
86. Staatz CE, Goodman LK, Tett SE. Effect of CYP3A and ABCB1 single nucleotide polymorphisms on the pharmacokinetics and pharmacodynamics of calcineurin inhibitors: Part I. Clin Pharmacokinet 2010; 49: 141-175 [PMID: 20170205 DOI: 10.2165/ 11317350-000000000-00000]
87. Hesselink DA, van Schaik RH, van Agteren M, de Fijter JW, Hartmann A, Zeier M, Budde K, Kuypers DR, Pisarski P, Le Meur Y, Mamelok RD, van Gelder T. CYP3A5 genotype is not associated with a higher risk of acute rejection in tacrolimus-treated renal transplant recipients. Pharmacogenet Genomics 2008; 18: 339-348 [PMID: 18334918 DOI: 10.1097/ FPC.0b013e3282f75f88]
88. Wei-lin W, Jing J, Shu-sen Z, Li-hua W, Ting-bo L, Song-feng Y, Sheng Y. Tacrolimus dose requirement in relation to donor and recipient ABCB1 and CYP3A5 gene polymorphisms in Chinese liver transplant patients. Liver Transpl 2006; 12: 775-780 [PMID: 16628701]
89. Li D, Zhu JY, Gao J, Wang X, Lou YQ, Zhang GL. Polymorphisms of tumor necrosis factor-alpha, interleukin-10, cytochrome P450 3A5 and ABCB1 in Chinese liver transplant patients treated with immunosuppressant tacrolimus. Clin Chim Acta 2007; 383: 133-139 [PMID: 17568575]
90. Fukudo M, Yano I, Yoshimura A, Masuda S, Uesugi M, Hosohata K, Katsura T, Ogura Y, Oike F, Takada Y, Uemoto S, Inui K. Impact of MDR1 and CYP3A5 on the oral clearance of tacrolimus and tacrolimus-related renal dysfunction in adult livingdonor liver transplant patients. Pharmacogenet Genomics 2008; 18: 413-423 [PMID: 18408564 DOI: 10.1097/FPC.0b013e3282f9ac01]
91. Provenzani A, Notarbartolo M, Labbozzetta M, Poma P, Biondi F, Sanguedolce R, Vizzini G, Palazzo U, Polidori P, Triolo F, Gridelli B, D'Alessandro N. The effect of CYP3A5 and ABCB1 single nucleotide polymorphisms on tacrolimus dose requirements in Caucasian liver transplant patients. Ann Transplant 2009; 14: 23-31 [PMID: 19289993]
92. Provenzani A, Notarbartolo M, Labbozzetta M, Poma P, Vizzini G, Salis P, Caccamo C, Bertani T, Palazzo U, Polidori P, Gridelli B, D'Alessandro N. Influence of CYP3A5 and ABCB1 gene polymorphisms and other factors on tacrolimus dosing in Caucasian liver and kidney transplant patients. Int J Mol Med 2011; 28: 1093-1102 [PMID: 21922127 DOI: 10.3892/ijmm.2011.794]
93. Provenzani A, Notarbartolo M, Labbozzetta M, Poma P, D' Antoni A, Polidori P, Vizzini G, D'Alessandro N. Unusual high dose of tacrolimus in liver transplant patient, a case report. Int J Clin Pharm 2012; 34: 269-271 [PMID: 22422348 DOI: 10.1007/ s11096-012-9622-6]
94. Barrera-Pulido L, Aguilera-García I, Docobo-Pérez F, Alamo-Martínez JM, Pareja-Ciuró F, Nuñez-Roldán A, Gómez-Bravo MA, Bernardos-Rodríguez A. Clinical relevance and prevalence of polymorphisms in CYP3A5 and MDR1 genes that encode tacrolimus biotransformation enzymes in liver transplant recipients. Transplant Proc 2008; 40: 2949-2951 [PMID: 19010156 DOI: 10.1016/j.transproceed.2008.09.016]
95. Chakkera HA, Chang YH, Bodner JK, Behmen S, Heilman RL, Reddy KS, Mulligan DC, Moss AA, Khamash H, Katariya N, Hewitt WR, Pitta TL, Frassetto LA. Genetic differences in Native Americans and tacrolimus dosing after kidney transplantation. Transplant Proc 2013; 45: 137-141 [PMID: 23375287 DOI: 10.1016/ j.transproceed.2012.10.023]
96. Glowacki F, Lionet A, Buob D, Labalette M, Allorge D, Provôt F, Hazzan M, Noël C, Broly F, Cauffiez C. CYP3A5 and ABCB1 polymorphisms in donor and recipient: impact on Tacrolimus dose requirements and clinical outcome after renal transplantation. Nephrol Dial Transplant 2011; 26: 3046-3050 [PMID: 21677300 DOI: 10.1093/ndt/gfr253]
97. López-Montenegro Soria MA, Kanter Berga J, Beltrán Catalán S, Milara Payá J, Pallardó Mateu LM, Jiménez Torres NV. Genetic polymorphisms and individualized tacrolimus dosing. Transplant Proc 2010; 42: 3031-3033 [PMID: 20970601]
98. Jun KR, Lee W, Jang MS, Chun S, Song GW, Park KT, Lee SG, Han DJ, Kang C, Cho DY, Kim JQ, Min WK. Tacrolimus concentrations in relation to CYP3A and ABCB1 polymorphisms among solid organ transplant recipients in Korea. Transplantation 2009; 87: 1225-1231 [PMID: 19384171 DOI: 10.1097/ TP.0b013e31819f117e]
99. Elens L, Capron A, Kerckhove VV, Lerut J, Mourad M, Lison D, Wallemacq P, Haufroid V. 1199G& gt; A and 2677G& gt; T/A polymorphisms of ABCB1 independently affect tacrolimus concentration in hepatic tissue after liver transplantation. Pharmacogenet Genomics 2007; 17: 873-883 [PMID: 17885626]
100. Macphee IA, Fredericks S, Mohamed M, Moreton M, Carter ND, Johnston A, Goldberg L, Holt DW. Tacrolimus pharmacogenetics: the CYP3A51 allele predicts low dose-normalized tacrolimus blood concentrations in whites and South Asians. Transplantation 2005; 79: 499-502 [PMID: 15729180]
101. Thervet E, Loriot MA, Barbier S, Buchler M, Ficheux M, Choukroun G, Toupance O, Touchard G, Alberti C, Le Pogamp P, Moulin B, Le Meur Y, Heng AE, Subra JF, Beaune P, Legendre C. Optimization of initial tacrolimus dose using pharmacogenetic testing. Clin Pharmacol Ther 2010; 87: 721-726 [PMID: 20393454 DOI: 10.1038/clpt.2010.17]
102. Spierings N, Holt DW, MacPhee IA. CYP3A5 genotype had no impact on intrapatient variability of tacrolimus clearance in renal transplant recipients. Ther Drug Monit 2013; 35: 328-331 [PMID: 23666583 DOI: 10.1097/FTD.0b013e318289644d]
103. Chen SY, Li JL, Meng FH, Wang XD, Liu T, Li J, Liu LS, Fu Q, Huang M, Wang CX. Individualization of tacrolimus dosage basing on cytochrome P450 3A5 polymorphism--a prospective, randomized, controlled study. Clin Transplant 2013; 27: E272-E281 [PMID: 23432535 DOI: 10.1111/ctr.12101]
104. Kuypers DR, Naesens M, de Jonge H, Lerut E, Verbeke K, Vanrenterghem Y. Tacrolimus dose requirements and CYP3A5 genotype and the development of calcineurin inhibitorassociated nephrotoxicity in renal allograft recipients. Ther Drug Monit 2010; 32: 394-404 [PMID: 20526235 DOI: 10.1097/ FTD.0b013e3181e06818]
105. Jacobson PA, Schladt D, Israni A, Oetting WS, Lin YC, Leduc R, Guan W, Lamba V, Matas AJ. Genetic and clinical determinants of early, acute calcineurin inhibitor-related nephrotoxicity: results from a kidney transplant consortium. Transplantation 2012; 93: 624-631 [PMID: 22334041 DOI: 10.1097/ TP.0b013e3182461288]
106. Kuypers DR, de Jonge H, Naesens M, Vanrenterghem Y. A prospective, open-label, observational clinical cohort study of the association between delayed renal allograft function, tacrolimus exposure, and CYP3A5 genotype in adult recipients. Clin Ther 2010; 32: 2012-2023 [PMID: 21118736 DOI: 10.1016/ j.clinthera.2010.11.010]
107. Chen Y, Sampaio MS, Yang JW, Min D, Hutchinson IV. Genetic polymorphisms of the transcription factor NFATc4 and development of new-onset diabetes after transplantation in Hispanic kidney transplant recipients. Transplantation 2012; 93: 325-330 [PMID: 22234350 DOI: 10.1097/TP.0b013e31823f7f26]
108. Huang N, Agrawal V, Giacomini KM, Miller WL. Genetics of P450 oxidoreductase: sequence variation in 842 individuals of four ethnicities and activities of 15 missense mutations. Proc Natl Acad Sci USA 2008; 105: 1733-1738 [PMID: 18230729 DOI:10.1073/pnas.0711621105]
109. Zhang JJ, Zhang H, Ding XL, Ma S, Miao LY. Effect of the P450 oxidoreductase 28 polymorphism on the pharmacokinetics of tacrolimus in Chinese healthy male volunteers. Eur J Clin Pharmacol 2013; 69: 807-812 [PMID: 23097010 DOI: 10.1007/ s00228-012-1432-1]
110. de Jonge H, Metalidis C, Naesens M, Lambrechts D, Kuypers DR. The P450 oxidoreductase28 SNP is associated with low initial tacrolimus exposure and increased dose requirements in CYP3A5-expressing renal recipients. Pharmacogenomics 2011; 12: 1281-1291 [PMID: 21770725 DOI: 10.2217/pgs.11.77]
111. Daly AK. Significance of the minor cytochrome P450 3A isoforms. Clin Pharmacokinet 2006; 45: 13-31 [PMID: 16430309]
112. Burk O, Tegude H, Koch I, Hustert E, Wolbold R, Glaeser H, Klein K, Fromm MF, Nuessler AK, Neuhaus P, Zanger UM, Eichelbaum M, Wojnowski L. Molecular mechanisms of polymorphic CYP3A7 expression in adult human liver and intestine. J Biol Chem 2002; 277: 24280-24288 [PMID: 11940601]
113. Sim SC, Edwards RJ, Boobis AR, Ingelman-Sundberg M. CYP3A7 protein expression is high in a fraction of adult human livers and partially associated with the CYP3A71C allele. Pharmacogenet Genomics 2005; 15: 625-631 [PMID: 16041241]
114. Knops N, Levtchenko E, van den Heuvel B, Kuypers D. From gut to kidney: transporting and metabolizing calcineurin-inhibitors in solid organ transplantation. Int J Pharm 2013; 452: 14-35 [PMID: 23711732 DOI: 10.1016/j.ijpharm.2013.05.033]
115. Shi XJ, Geng F, Jiao Z, Cui XY, Qiu XY, Zhong MK. Association of ABCB1, CYP3A418B and CYP3A53 genotypes with the pharmacokinetics of tacrolimus in healthy Chinese subjects: a population pharmacokinetic analysis. J Clin Pharm Ther 2011; 36: 614-624 [PMID: 21916909 DOI: 10.1111/j.1365]
116. Li DY, Teng RC, Zhu HJ, Fang Y. CYP3A4/5 polymorphisms affect the blood level of cyclosporine and tacrolimus in Chinese renal transplant recipients. Int J Clin Pharmacol Ther 2013; 51: 466-474 [PMID: 23557867 DOI: 10.5414/CP201836]
117. Elens L, van Gelder T, Hesselink DA, Haufroid V, van Schaik RH. CYP3A422: promising newly identified CYP3A4 variant allele for personalizing pharmacotherapy. Pharmacogenomics 2013; 14: 47-62 [PMID: 23252948 DOI: 10.2217/pgs.12.187]
118. Elens L, Bouamar R, Hesselink DA, Haufroid V, van der Heiden IP, van Gelder T, van Schaik RH. A new functional CYP3A4 intron 6 polymorphism significantly affects tacrolimus pharmacokinetics in kidney transplant recipients. Clin Chem 2011; 57: 1574-1583 [PMID: 21903774 DOI: 10.1373/clinchem.2011.165613]
119. Wang D, Guo Y, Wrighton SA, Cooke GE, Sadee W. Intronic polymorphism in CYP3A4 affects hepatic expression and response to statin drugs. Pharmacogenomics J 2011; 11: 274-286 [PMID: 20386561 DOI: 10.1038/tpj.2010.28]
120. Okubo M, Murayama N, Shimizu M, Shimada T, Guengerich FP, Yamazaki H. CYP3A4 intron 6 C& gt; T polymorphism (CYP3A422) is associated with reduced CYP3A4 protein level and function in human liver microsomes. J Toxicol Sci 2013; 38: 349-354 [PMID: 23665933]
121. Santoro AB, Struchiner CJ, Felipe CR, Tedesco-Silva H, Medina-Pestana JO, Suarez-Kurtz G. CYP3A5 genotype, but not CYP3A41b, CYP3A422, or hematocrit, predicts tacrolimus dose requirements in Brazilian renal transplant patients. Clin Pharmacol Ther 2013; 94: 201-202 [PMID: 23588314 DOI: 10.1038/ clpt.2013.68]
122. Smith HE, Jones JP, Kalhorn TF, Farin FM, Stapleton PL, Davis CL, Perkins JD, Blough DK, Hebert MF, Thummel KE, Totah RA. Role of cytochrome P450 2C8 and 2J2 genotypes in calcineurin inhibitor-induced chronic kidney disease. Pharmacogenet Genomics 2008; 18: 943-953 [PMID: 18769365 DOI: 10.1097/ FPC.0b013e32830e1e16]
123. Gervasini G, Garcia M, Macias RM, Benitez J, Caravaca F, Cubero JJ. CYP2C83 polymorphism and donor age are associated with allograft dysfunction in kidney transplant recipients treated with calcineurin inhibitors. J Clin Pharmacol 2013; 53: 427-434 [PMID: 23426640 DOI: 10.1002/jcph.15]
124. Wagner K, Webber SA, Kurland G, Boyle GJ, Miller SA, Cipriani L, Griffith BP, Fricker FJ. New-onset diabetes mellitus in pediatric thoracic organ recipients receiving tacrolimus-based immunosuppression. J Heart Lung Transplant 1997; 16: 275-282 [PMID: 9087870]
125. Ippoliti GB, Viganò M. [Calcineurin inhibitors and mechanisms that are responsible for the appearance of post-transplant diabetes mellitus]. G Ital Nefrol 2003; 20 Suppl 25: S11-S14 [PMID: 14523907]
126. Lee Sr, Moon JY, Lee SH, Ihm CG, Lee TW, Kim SK, Chung JH, Kang SW, Kim TH, Park SJ, Kim YH, Jeong KH. Angiotensinogen polymorphisms and post-transplantation diabetes mellitus in Korean renal transplant subjects. Kidney Blood Press Res 2013; 37: 95-102 [PMID: 23594830 DOI: 10.1159/000343404]
127. Inoue I, Nakajima T, Williams CS, Quackenbush J, Puryear R, Powers M, Cheng T, Ludwig EH, Sharma AM, Hata A, Jeunemaitre X, Lalouel JM. A nucleotide substitution in the promoter of human angiotensinogen is associated with essential hypertension and affects basal transcription in vitro. J Clin Invest 1997; 99: 1786-1797 [PMID: 9120024]
128. Kim HS, Krege JH, Kluckman KD, Hagaman JR, Hodgin JB, Best CF, Jennette JC, Coffman TM, Maeda N, Smithies O. Genetic control of blood pressure and the angiotensinogen locus. Proc Natl Acad Sci USA 1995; 92: 2735-2739 [PMID: 7708716]