Impact of PPARA and POR polymorphisms on tacrolimus pharmacokinetics and new-onset diabetes in kidney transplant recipients

Pharmacogenetics and Genomics

Volumn 24, Issue 8, 2014, Pages 397-400

  Kurzawski, Mateusz ^a   Malinowski, Damian ^a   Dziewanowski, Krzysztof ^b   Droździk, Marek ^a  

^a POMERANIAN MEDICAL UNIVERSITY   (Poland)

^b Marie Curie Regional Hospital   (Poland)

Author keywords

kidney transplantation; pharmacogenetics; POR; PPARA; tacrolimus

Indexed keywords

CYTOCHROME P450 3A4; CYTOCHROME P450 3A5; CYTOCHROME P450 REDUCTASE; GLUCOSE; INSULIN; ORAL ANTIDIABETIC AGENT; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; TACROLIMUS;

ALLELE; ARTICLE; DIABETES MELLITUS; GENETIC ASSOCIATION; GENETIC MARKER; GENOTYPE; GLUCOSE BLOOD LEVEL; GRAFT RECIPIENT; HETEROZYGOTE; HOMOZYGOTE; HUMAN; KIDNEY GRAFT; MAJOR CLINICAL STUDY; NEW ONSET DIABETES AFTER TRANSPLANTATION; PRIORITY JOURNAL; SINGLE NUCLEOTIDE POLYMORPHISM;

ADOLESCENT; ADULT; AGED; ALLELES; CYTOCHROME P-450 ENZYME SYSTEM; DIABETES COMPLICATIONS; DIABETES MELLITUS; FEMALE; GENOTYPE; HETEROZYGOTE; HOMOZYGOTE; HUMANS; KIDNEY FAILURE, CHRONIC; KIDNEY TRANSPLANTATION; MALE; MIDDLE AGED; MULTIVARIATE ANALYSIS; PHARMACOGENETICS; POLYMORPHISM, GENETIC; PPAR ALPHA; RISK FACTORS; TACROLIMUS;

EID: 84904270367     PISSN: 17446872     EISSN: 17446880     Source Type: Journal    
DOI: 10.1097/FPC.0000000000000067     Document Type: Article

References (15)

1. Kurzawski M, Droździk M. Pharmacogenetics in solid organ transplantation: genes involved in mechanism of action and pharmacokinetics of immunosuppressive drugs. Pharmacogenomics 2013; 14:1099-1118.
2. Terrazzino S, Quaglia M, Stratta P, Canonico PL, Genazzani AA. The effect of CYP3A5 6986A G and ABCB1 3435C T on tacrolimus doseadjusted trough levels and acute rejection rates in renal transplant patients: a systematic review and meta-analysis. Pharmacogenet Genomics 2012; 22:642-645.
3. Tavira B, Coto E, Diaz-Corte C, Alvarez V, López-Larrea C, Ortega F. A search for new CYP3A4 variants as determinants of tacrolimus dose requirements in renal-transplanted patients. Pharmacogenet Genomics 2013; 23:445-448.
4. Elens L, van Schaik RH, Panin N, de Meyer M, Wallemacq P, Lison D, et al. Effect of a new functional CYP3A4 polymorphism on calcineurin inhibitors' dose requirements and trough blood levels in stable renal transplant patients. Pharmacogenomics 2011; 12:1383-1396.
5. Klein K, Zanger UM. Pharmacogenomics of cytochrome P450 3A4: recent progress toward the "Missing Heritability" problem. Front Genet 2013; 4:12.
6. Klein K, Thomas M, Winter S, Nussler AK, Niemi M, Schwab M, Zanger UM. PPARA: a novel genetic determinant of CYP3A4 in vitro and in vivo. Clin Pharmacol Ther 2012; 91:1044-1052.
7. De Jonge H, Metalidis C, Naesens M, Lambrechts D, Kuypers DRJ. The P450 oxidoreductase*28 SNP is associated with low initial tacrolimus exposure and increased dose requirements in CYP3A5-expressing renal recipients. Pharmacogenomics 2011; 12:1281-1291.
8. 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.
9. Miller WL, Agrawal V, Sandee D, Tee MK, Huang N, Choi JH, et al. Consequences of POR mutations and polymorphisms. Mol Cell Endocrinol 2011; 336:174-179.
10. Elens L, Hesselink DA, Bouamar R, Budde K, de Fijter JW, De Meyer M, et al. Impact of POR*28 on the pharmacokinetics of tacrolimus and cyclosporine a in renal transplant patients. Ther Drug Monit 2014; 36:71-79.
11. Elens L, Sombogaard F, Hesselink DA, van Schaik RH, van Gelder T. Single-nucleotide polymorphisms in P450 oxidoreductase and peroxisome proliferator-activated receptor-alpha are associated with the development of new-onset diabetes after transplantation in kidney transplant recipients treated with tacrolimus. Pharmacogenet Genomics 2013; 23:649-657.
12. Kurzawski M, D?browska J, Dziewanowski K, Doma?ski L, Peru?y?ska M, Droździk M. CYP3A5 and CYP3A4, but not ABCB1 polymorphisms affect tacrolimus dose adjusted trough concentration in kidney transplant recipients. Pharmacogenomics 2014; 15:179-188.
13. De Keyser CE, Becker ML, Uitterlinden AG, Hofman A, Lous JJ, Elens L, et al. Genetic variation in the PPARA gene is associated with simvastatinmediated cholesterol reduction in the Rotterdam study. Pharmacogenomics 2013; 14:1295-1304.
14. Hu M, Mak VW, Xiao Y, Tomlinson B. Associations between the genotypes and phenotype of CYP3A and the lipid response to simvastatin in Chinese patients with hypercholesterolemia. Pharmacogenomics 2013; 14:25-34.
15. Woillard JB, Kamar N, Coste S, Rostaing L, Marquet P, Picard N. Effect of CYP3A4*22, POR*28, and PPARA rs4253728 on sirolimus in vitro metabolism and trough concentrations in kidney transplant recipients. Clin Chem 2013; 59:1761-1769.