SLCO1B1 genetic polymorphism influences mycophenolic acid tolerance in renal transplant recipients. (December 2010)

• Record Type: Journal Article
• Authors: Michelon, Hugues; König, Jörg; Durrbach, Antoine; Quteineh, Lina; Verstuyft, Céline; Furlan, Valérie; Ferlicot, Sophie; Letierce, Alexia; Charpentier, Bernard; Fromm, Martin F; Becquemont, Laurent
• Is Part Of: Pharmacogenomics. Volume 11:Number 12(2010)
• Page Start: 1703
• Page End: 1713
• Publication Date: 2010-12
• Subjects: adverse drug reaction -- genetic polymorphism -- mycophenolic acid -- OATP1B1 -- pharmacogenetics -- renal transplantation -- SLCO1B1; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs.10.132
• Languages: English
• ISSNs: 1462-2416

Abstract

Aims: This study aimed to determine the influence of gene candidates on mycophenolic acid (MPA) response during the first year of renal transplantation.Materials & methods: A total of 218 renal transplant recipients who received MPA from the first day of transplantation at a fixed dose of 2 g/day were genotyped for ABCB1, ABCC2, UGT2B7, UGT1A9, SLCO1B1, SLCO1B3 and IMPDH1 polymorphisms. Clinical end points were MPA-related adverse drug reactions (ADRs) and acute rejection episodes during the first year post-transplantation.Results: After correction for multiple statistical testing, SLCO1B1 (encoding the hepatic uptake transporter OATP1B1) was the only gene associated with MPA-related ADRs, showing a 75% risk reduction in favor of a protective effect of the SLCO1B1*5 allele (p = 0.002). In vitro experiments showed that MPA metabolites MPA-phenyl-glucuronide and MPA-acyl-glucuronide are substrates of OATP1B1. Their transport was decreased in the presence of the variant transporter (OATP1B1*5).Conclusion: These results suggest for the first time that carriers of the SLCO1B1*5 allele seem to be protected from MPA-related ADRs.