Genome-wide association study to characterize serum bilirubin elevations in patients with HCV treated with GS-9256, an HCV NS3 serine protease inhibitor

Antiviral Therapy

Volumn 19, Issue 7, 2014, Pages 679-686

  Nelson, David ^a   Yoshida, Eric M ^b   Paulson, Matthew S ^c   Hengen, Paul N ^c   Ge, Dongliang ^c   Kanwar, Bittoo ^c   McNally, John ^c   Pang, Phillip S ^c   Subramanian, G Mani ^c   McHutchison, John G ^c   Urbanek, Petr ^d   Lawitz, Eric ^e   Urban, Thomas J ^f,g  

^a UNIVERSITY OF FLORIDA COLLEGE OF MEDICINE   (United States)

^b UNIVERSITY OF BRITISH COLUMBIA   (Canada)

^c GILEAD SCIENCES   (United States)

^d CHARLES UNIVERSITY   (Czech Republic)

^e Alamo Medical Research   (United States)

^f DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^g UNIVERSITY OF NORTH CAROLINA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BILIRUBIN; GS 9256; ORGANIC ANION TRANSPORTER B; PEGINTERFERON; RIBAVIRIN; SOLUTE CARRIER ORGANIC ANION TRANSPORTER 1B1; SOLUTE CARRIER ORGANIC ANION TRANSPORTER 1B3; TEGOBUVIR; ANTIVIRUS AGENT; CYCLOPEPTIDE; GS-9256; NS3 PROTEIN, HEPATITIS C VIRUS; ORGANIC ANION TRANSPORTER; PHOSPHINIC ACID DERIVATIVE; SLCO1B1 PROTEIN, HUMAN; SLCO1B3 PROTEIN, HUMAN; VIRUS PROTEIN;

ADULT; AGED; ARTICLE; CONTROLLED STUDY; FEMALE; GENETIC ASSOCIATION; GENETIC MARKER; GENETIC VARIABILITY; HEPATITIS C; HEPATITIS C VIRUS GENOTYPE 1; HUMAN; HYPERBILIRUBINEMIA; MAJOR CLINICAL STUDY; MALE; OATP1B1 GENE; OATP1B3 GENE; OATP2B1 GENE; QUANTITATIVE TRAIT LOCUS MAPPING; SINGLE NUCLEOTIDE POLYMORPHISM; ANTAGONISTS AND INHIBITORS; BIOLOGY; BLOOD; DRUG EFFECTS; GENETICS; GENOTYPE; HEPACIVIRUS; METABOLISM; MICROBIAL SENSITIVITY TEST; MIDDLE AGED; PHARMACOGENETICS; PHENOTYPE; YOUNG ADULT;

ADULT; AGED; ANTIVIRAL AGENTS; BILIRUBIN; COMPUTATIONAL BIOLOGY; FEMALE; GENOME-WIDE ASSOCIATION STUDY; GENOTYPE; HEPACIVIRUS; HEPATITIS C; HUMANS; MALE; MICROBIAL SENSITIVITY TESTS; MIDDLE AGED; ORGANIC ANION TRANSPORTERS; ORGANIC ANION TRANSPORTERS, SODIUM-INDEPENDENT; PEPTIDES, CYCLIC; PHARMACOGENETICS; PHENOTYPE; PHOSPHINIC ACIDS; POLYMORPHISM, SINGLE NUCLEOTIDE; VIRAL NONSTRUCTURAL PROTEINS; YOUNG ADULT;

EID: 84920174789     PISSN: 13596535     EISSN: 20402058     Source Type: Journal    
DOI: 10.3851/IMP2747     Document Type: Article

References (28)

1. Zeuzem S, Assselah T, Angus P, et al. Efficacy of the protease inhibitor BI 201335, polymerase inhibitor BI 207127, and ribavirin in patients with chronic HCV infection. Gastroenterology 2011; 141:2047-2055.
2. Yang J, Yang C, Mathias A, et al. In vitro inhibition of hepatic bilirubin transporters by the HCV NS3 protease inhibitor GS-9451 and in vivo correlation in healthy subjects. 47th Annual Meeting of the European Association for the Study of the Liver. 18-22 April 2012, Barcelona, Spain. Abstract 1216.
3. Huisman MT, Snoeys J, Monbaliu J, Martens M, Sekar V, Raoof A. In vitro studies investigating the mechanism of interaction between TMC435 and hepatic transporters. 61st Annual Meeting of the American Association for the Study of Liver Diseases. 29 October-2 November 2010, Boston, MA, USA. Abstract 278.
4. Campbell SD, de Morais SM, Xu JJ. Inhibition of human organic anion transporting polypeptide OATP 1B1 as a mechanism of drug-induced hyperbilirubinemia. Chem Biol Interact 2004; 150:179-187.
5. Guidance for Industry. Drug-Induced Liver Injury: Premarketing Clinical Evaluation. Department of Health and Human Services. (Updated July 2009. Accessed 26 February 2013.) Available from http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM174090.pdf
6. Fellay J, Thompson AJ, Ge D, et al. ITPA gene variants protect against anaemia in patients treated for chronic hepatitis C. Nature 2010; 464:405-408.
7. Chen G, Ramos E, Adeyemo A, et al. UGT1A1 is a major locus influencing bilirubin levels in African Americans. Eur J Hum Genet 2012; 20:463-468.
8. Johnson AD, Kavousi M, Smith AV, et al. Genome-wide association meta-analysis for total serum bilirubin levels. Hum Mol Genet 2009; 18:2700-2710.
9. Sanna S, Busonero F, Maschio A, et al. Common variants in the SLC01B3 locus are associated with bilirubin levels and unconjugated hyperbilirubinemia. Hum Mol Genet 2009; 18:2711-2718.
10. Nakanishi T, Tamai I. Genetic polymorphisms of OATP transporters and their impact on intestinal absorption and hepatic disposition of drugs. Drug Metab Pharmacokinet 2012; 27:106-121.
11. Nozawa T, Minami H, Sugiura S, Tsuji A, Tamai I. Role of organic anion transporter OATP1B1 (OATP-C) in hepatic uptake of irinotecan and its active metabolite, 7-ethyl-10-hydroxycamptothecin: in vitro evidence and effect of single nucleotide polymorphisms. Drug Metab Dispos 2005; 33:434-439.
12. Takane H, Kawamoto K, Sasaki T, et al. Life-threatening toxicities in a patient with UGT1A1∗6/∗28 and SLCO1B1∗15/∗15 genotypes after irinotecan-based chemotherapy. Cancer Chemother Pharmacol 2009; 63:1165-1169.
13. Kweekel D, Guchelaar HJ, Gelderblom H. Clinical and pharmacogenetic factors associated with irinotecan toxicity. Cancer Treat Rev 2008; 34:656-669.
14. Zeuzem S, Buggisch P, Agarwal K, et al. The protease inhibitor, GS-9256, and non-nucleoside polymerase inhibitor tegobuvir alone, with ribavirin, or pegylated interferon plus ribavirin in hepatitis C. Hepatology 2012; 55:749-758.
15. Tong L, Mwangi J, Roy A, et al. In vitro studies on the potential for the hepatitis C virus protease inhibitors GS-9256 and GS-9451 to affect bilirubin elimination. 46th Annual Meeting of the European Association for the Study of the Liver. 30 March-3 April 2011, Berlin, Germany. Abstract 1232.
16. Sane R, Podila L, Mathur K, et al. Mechanisms of isolated unconjugated hyperbilirubinemia induced by the HCV NS3/4A protease inhibitor BI201335. 46th Annual Meeting of the European Association for the Study of the Liver. 30 March-3 April 2011, Berlin, Germany. Abstract 1236.
17. Nelson DR, Lawitz E, Bain V, et al. High SVR12 with 16 weeks of tegobuvir and GS-9256 with peginterferon-alfa 2a and ribavirin in treatment-naive genotype 1 HCV patients. 47th Annual Meeting of the European Association for the Study of the Liver. 18-22 April 2012, Barcelona, Spain. Abstract 12.
18. Purcell S, Neale B, Todd-Brown K, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007; 81:559-575.
19. Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005; 21:263-265.
20. McCarthy MI, Abecasis GR, Cardon LR, et al. Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat Rev Genet 2008; 9:356-369.
21. Price AL, Patterson NJ, Pleng RM, Weinblatt ME, Shadick NA, Reich D. Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 2006; 38:904-909.
22. Sulkowski MS, Asselah T, Lalezari J, et al. Faldaprevir combined with pegylated interferon alfa-2a and ribavirin in treatment-naïve patients with chronic genotype1 HCV: SILEN-C1 trial. Hepatology 2013; 57:2143-2154.
23. Fried M, Poordad F, Zeuzem S, et al. Safety and tolerability of TMC435 in combination with peginterferon alpha-2a and ribavirin for treatment of HCV genotype 1 infection in treatment-naive and -experienced patients (PILLAR and ASPIRE trials). 63rd Annual Meeting of the American Association for the Study of Liver Diseases. 9-13 November 2012, Boston, MA, USA. Abstract 769.
24. Poordad F, Fried M, Zeuzem S, et al. Efficacy and tolerability of TMC435 150 mg once daily with peginterferon alpha-2a and ribavirin for treatment of HCV genotype 1 infection in patients with Metavir score F3 and F4 (PILLAR and ASPIRE trials). 63rd Annual Meeting of the American Association for the Study of Liver Diseases. 9-13 November 2012, Boston, MA, USA. Abstract 83.
25. Tirona RG, Leake BF, Merino G, Kim RB. Polymorphisms in OATP-C. J Biol Chem 2001; 276:35669-35675.
26. Kameyama Y, Yamashita K, Kobayashi Y, Hosokawa M, Chiba K. 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. Pharmacogenet Genomics 2005; 15:513-522.
27. SEARCH Collaborative Group, Link E, Parish S, et al. SLCO1B1 variants and statin-induced myopathy - a genomewide study. N Engl J Med 2008; 359:789-799.
28. Ge D, Fellay J, Thompson AJ, et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 2009; 461:399-401.