The relationship between main transporter pharmacogenetics and statin efficacy

Abstract

Abstract: Organic anion-transporting polypeptide 1B1 and breast cancer-resistance protein are the important transporters in human, participating in absorption, distribution and excretion of many substances including statins. However, researchers had paid more attention on the metabolic enzymes in the pharmacokinetics and pharmacodynamics, the studies on transporters is lagged behind of metabolic enzymes. With the development of science, we got to focus on the role of transporters on the statin toxicity recently. This paper is to review the relationship between the main transporter pharmacogenetics and statin efficacy.

Key words: OATP1B1, ABCG2, Statins

CLC Number:

R968

WANG Li-ping, SONG Jin-chun. The relationship between main transporter pharmacogenetics and statin efficacy[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(3): 344-350.

References

[1] Baer CF, Miyamoto MM, Denver DR. Mutation rate variation in multicellular eukaryotes: causes and consequences[J]. Nat Rev Genet, 2007, 8(8): 619-631.
[2] Christopher-Stine L. Statin myopathy: an update[J]. Curr Opin Rheumatol, 2006, 18(6): 647-653.
[3] 阿托伐他汀对冠状动脉斑块退缩及其成分的影响[J]. 中国临床药理学与治疗学, 2009, 14(4): 438.
[4] Sirvent P, Mercier J, Lacampagne A. New insights into mechanisms of statin-associated myotoxicity[J]. Curr Opin Pharmacol, 2008, 8(3): 333-338.
[5] Niemi M. Transporter pharmacogenetics and statin toxicity[J]. Clin Pharmacol Ther, 2010, 87(1): 130- 133.
[6] 殷晓伟, 胡厚源, 杨庭树, 等. 长期应用他汀类药物对合并高血糖心肌梗死病人血脂及左室功能的影响[J]. 中国临床药理学与治疗学, 2007, 12(5): 597.
[7] Hodel C. Myopathy and rhabdomyolysis with lipid-lowering drugs[J]. Toxicol Lett, 2002, 128(1/2/3): 159-168.
[8] Antons KA, Williams CD, Baker SK, et al. Clinical perspectives of statin-induced rhabdomyolysis[J]. Am J Med, 2006, 119(5): 400-409.
[9] Sinzinger H, Chehne F, Lupattelli G. Oxidation injury in patients receiving HMG-CoA reductase inhibitors: occurrence in patients without enzyme elevation or myopathy[J]. Drug Saf, 2002, 25(12): 877-883.
[10] Riesco-Eizaguirre G, Arpa-Gutierrez FJ, Gutierrez M, et al. Severe polymyositis with simvastatin use[J]. Rev Neurol, 2003, 37(10): 934-936.
[11] Langford NJ, Kendall MJ. Rhabdomyolysis with HMG CoA reductase inhibitors: a class effect[J] ? J Clin Pharm Ther, 2001, 26(6): 391-395.
[12] Nishizato Y, Ieiri I, Suzuki H, et al. Polymorphisms of OATP-C (SLC21A6) and OAT3 (SLC22A8) genes: consequences for pravastatin pharmacokinetics[J]. Clin Pharmacol Ther, 2003, 73(6): 554-565.
[13] Niemi M. Transporter pharmacogenetics and statin toxicity[J]. Clin Pharmacol Ther, 2010, 87(1): 130-133.
[14] Cusatis G, Sparreboom A. Pharmacogenomic importance of ABCG2[J]. Pharmacogenomics, 2008, 9(8): 1005-1009.
[15] Hsiang B, Zhu Y, Wang Z, et al. A novel human hepatic organic anion transporting polypeptide (OATP2). Identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters[J]. J Biol Chem, 1999, 274(52): 37161-37168.
[16] Shitara Y, Itoh T, Sato H, et al. Inhibition of transporter-mediated hepatic uptake as a mechanism for drug-drug interaction between cerivastatin and cyclosporin A[J]. J Pharmacol Exp Ther, 2003, 304(2): 610-616.
[17] Pasanen MK, Miettinen TA, Gylling H, et al. Polymorphism of the hepatic influx transporter organic anion transporting polypeptide 1B1 is associated with increased cholesterol synthesis rate[J]. Pharmacogenet Genomics, 2008, 18(10): 921-926.
[18] Tamai I, Nezu J, Uchino H, et al. Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family[J]. Biochem Biophys Res Commun, 2000, 273(1): 251-260.
[19] Tirona RG, Leake BF, Merino G, et al. Polymorphisms in OATP-C: identification of multiple allelic variants associated with altered transport activity among European- and African-Americans[J]. J Biol Chem, 2001, 276(38): 35669-35675.
[20] Tirona RG, Leake BF, Wolkoff AW, et al. Human organic anion transporting polypeptide-C (SLC21A6) is a major determinant of rifampin-mediated pregnane X receptor activation[J]. J Pharmacol Exp Ther, 2003, 304(1): 223-228.
[21] Kameyama Y, Yamashita K, Kobayashi K, et al. Functional characterization of SLCO1B1 (OATP-C) variants, SLCO1B1*5, SLCO1B1*15 and SLCO1B1*15+C1007G, by using transient expression systems of HeLa and HEK293 cells[J]. Pharmacogenet Genomics, 2005, 15(7): 513-522.
[22] Niemi M. Role of OATP transporters in the disposition of drugs[J]. Pharmacogenomics, 2007, 8(7): 787-802.
[23] Tirona RG, Leake BF, Merino G, et al. Polymorphisms in OATP-C: identification of multiple allelic variants associated with altered transport activity among European- and African-Americans[J]. J Biol Chem, 2001, 276(38): 35669-35675.
[24] Niemi M, Pasanen MK, Neuvonen PJ. SLCO1B1 polymorphism and sex affect the pharmacokinetics of pravastatin but not fluvastatin[J]. Clin Pharmacol Ther, 2006, 80(4): 356-366.
[25] Jada SR, Xiaochen S,Yan LY, et al. Pharmacogenetics of SLCO1B1: haplotypes, htSNPs and hepatic expression in three distinct Asian populations[J]. Eur J Clin Pharmacol, 2007, 63(6): 555-563.
[26] Nishizato Y, Ieiri I, Suzuki H, et al. Polymorphisms of OATP-C (SLC21A6) and OAT3 (SLC22A8) genes: consequences for pravastatin pharmacokinetics[J]. Clin Pharmacol Ther, 2003, 73(6): 554-565.
[27] Niemi M, Schaeffeler E, Lang T, et al. High plasma pravastatin concentrations are associated with single nucleotide polymorphisms and haplotypes of organic anion transporting polypeptide-C (OATP-C, SLCO1B1)[J]. Pharmacogenetics, 2004, 14(7): 429-440.
[28] Seithel A, Eberl S, Singer K, et al. The influence of macrolide antibiotics on the uptake of organic anions and drugs mediated by OATP1B1 and OATP1B3[J]. Drug Metab Dispos, 2007, 35(5): 779-786.
[29] Tirona RG, Leake BF, Merino G, et al. Polymorphisms in OATP-C: identification of multiple allelic variants associated with altered transport activity among European- and African-Americans[J]. J Biol Chem, 2001, 276(38): 35669-35675.
[30] Pasanen MK, Fredrikson H, Neuvonen PJ, et al. Different effects of SLCO1B1 polymorphism on the pharmacokinetics of atorvastatin and rosuvastatin[J]. Clin Pharmacol Ther, 2007, 82(6): 726-733.
[31] Kim RB. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) and genetic variability (single nucleotide polymorphisms) in a hepatic drug uptake transporter: what's it all about[J] ? Clin Pharmacol Ther, 2004, 75(5): 381-385.
[32] Iwai M, Suzuki H, Ieiri I, et al. Functional analysis of single nucleotide polymorphisms of hepatic organic anion transporter OATP1B1 (OATP-C)[J]. Pharmacogenetics, 2004, 14(11): 749-757.
[33] Choi JH, Lee MG, Cho JY, et al. Influence of OATP1B1 genotype on the pharmacokinetics of rosuvastatin in Koreans[J]. Clin Pharmacol Ther, 2008, 83(2): 251-257.
[34] Link E, Parish S, Armitage J, et al. SLCO1B1 variants and statin-induced myopathy--a genomewide study[J]. N Engl J Med, 2008, 359(8): 789-799.
[35] Voora D, Shah SH, Spasojevic I, et al. The SLCO1B1*5 genetic variant is associated with statin-induced side effects[J]. J Am Coll Cardiol, 2009, 54(17): 1609.
[36] Doyle L A, Yang W, Abruzzo LV, et al. A multidrug resistance transporter from human MCF-7 breast cancer cells[J]. Proc Natl Acad Sci USA,1998, 95(26): 15665-15670.
[37] Allikmets R, Schriml LM, Hutchinson A, et al. A human placenta-specific ATP-binding cassette gene (ABCP) on chromosome 4q22 that is involved in multidrug resistance[J]. Cancer Res, 1998, 58(23): 5337- 5339.
[38] Miyake K, Mickley L, Litman T, et al. Molecular cloning of cDNAs which are highly overexpressed in mitoxantrone-resistant cells: demonstration of homology to ABC transport genes[J]. Cancer Res, 1999, 59(1): 8-13.
[39] Zhang JT. Biochemistry and pharmacology of the human multidrug resistance gene product, ABCG2[J]. Zhong Nan Da Xue Xue Bao Yi Xue Ban, 2007, 32(4): 531-541.
[40] Keskitalo JE, Zolk O, Fromm MF, et al. ABCG2 polymorphism markedly affects the pharmacokinetics of atorvastatin and rosuvastatin[J]. Clin Pharmacol Ther, 2009, 86(2): 197-203.
[41] Nicolle E, Boumendjel A, Macalou S, et al. QSAR analysis and molecular modeling of ABCG2-specific inhibitors[J]. Adv Drug Deliv Rev, 2009, 61(1): 34-46.
[42] Mizuno T, Terada T, Kamba T, et al. ABCG2 421C>A polymorphism and high exposure of sunitinib in a patient with renal cell carcinoma[J]. Ann Oncol, 2010, 21(6): 1382-1383.
[43] Kondo C, Suzuki H, Itoda M, et al. Functional analysis of SNPs variants of BCRP/ABCG2[J]. Pharm Res, 2004, 21(10): 1895-1903.
[44] Zhang W, Yu BN, He YJ, et al. Role of BCRP 421C>A polymorphism on rosuvastatin pharmacokinetics in healthy Chinese males[J]. Clin Chim Acta, 2006, 373(1/2): 99-103.
[45] Noguchi K, Katayama K, Mitsuhashi J, et al. Functions of the breast cancer resistance protein (BCRP/ABCG2) in chemotherapy[J]. Adv Drug Deliv Rev, 2009, 61(1): 26-33.
[46] Mao Q. BCRP/ABCG2 in the placenta: expression, function and regulation[J]. Pharm Res, 2008, 25(6): 1244-1255.
[47] Gradhand U, Kim RB. Pharmacogenomics of MRP transporters (ABCC1-5) and BCRP (ABCG2)[J]. Drug Metab Rev, 2008, 40(2): 317-354.
[48] Fujino H, Yamada I, Shimada S, et al. Metabolic fate of pitavastatin, a new inhibitor of HMG-CoA reductase: human UDP-glucuronosyltransferase enzymes involved in lactonization[J]. Xenobiotica, 2003, 33(1): 27.
[49] Zaher H, Meyer ZSH, Tirona RG, et al. Targeted disruption of murine organic anion-transporting polypeptide 1b2 (Oatp1b2/Slco1b2) significantly alters disposition of prototypical drug substrates pravastatin and rifampin[J]. Mol Pharmacol, 2008, 74(2): 320.
[50] Ide T, Sasaki T, Maeda K, et al. Quantitative population pharmacokinetic analysis of pravastatin using an enterohepatic circulation model combined with pharmacogenomic Information on SLCO1B1 and ABCC2 polymorphisms[J]. J Clin Pharmacol, 2009, 49(11): 1309.
[51] Hoenig MR, Walker PJ, Gurnsey C, et al. The C3435T polymorphism in ABCB1 influences atorvastatin efficacy and muscle symptoms in a high-risk vascular cohort[J]. J Clin Lipidol, 2011, 5(2): 91.
[52] Schwarz UI, Meyer ZSH, Tirona RG, et al. Identification of novel functional organic anion-transporting polypeptide 1B3 polymorphisms and assessment of substrate specificity[J]. Pharmacogenet Genomics, 2011, 21(3): 103.
[53] Allen RM, Marquart TJ, Albert CJ, et al. miR-33 controls the expression of biliary transporters, and mediates statin- and diet-induced hepatotoxicity[J]. EMBO Mol Med, 2012, 4(9): 882.
[54] Hu M, Tomlinson B. Effects of statin treatments and polymorphisms in UGT1A1 and SLCO1B1 on serum bilirubin levels in Chinese patients with hypercholesterolaemia[J]. Atherosclerosis, 2012, 223(2): 427.
[55] Knauer MJ, Urquhart BL, Meyer ZSH, et al. Human skeletal muscle drug transporters determine local exposure and toxicity of statins[J]. Circ Res, 2010, 106(2): 297.
[56] Yang SH, Choi JS, Choi DH. Effects of HMG-CoA reductase inhibitors on the pharmacokinetics of losartan and its main metabolite EXP-3174 in rats: possible role of CYP3A4 and P-gp inhibition by HMG-CoA reductase inhibitors[J]. Pharmacology, 2011, 88(1/2): 1-9.
[57] Li J, Volpe DA, Wang Y, et al. Use of transporter knockdown Caco-2 cells to investigate the in vitro efflux of statin drugs[J]. Drug Metab Dispos, 2011, 39(7): 1196-1202.
[58] Allen RM, Marquart TJ, Albert CJ, et al. miR-33 controls the expression of biliary transporters, and mediates statin- and diet-induced hepatotoxicity[J]. EMBO Mol Med, 2012, 4(9): 882-895.
[59] Rodrigues AC, Curi R, Genvigir FD, et al. The expression of efflux and uptake transporters are regulated by statins in Caco-2 cells[J]. Acta Pharmacol Sin, 2009,30(7):956-964.
[60] Yabuuchi H, Tanaka K, Maeda M, et al. Cloning of the dog bile salt export pump (BSEP; ABCB11) and functional comparison with the human and rat proteins[J]. Biopharm Drug Dispos, 2008, 29(8): 441-448.