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.
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.
Authors: Megan V Yanik; Michael E Seifert; Jayme E Locke; Vera Hauptfeld-Dolejsek; Michael R Crowley; Gary R Cutter; Roslyn B Mannon; Daniel I Feig; Nita A Limdi Journal: Pediatr Transplant Date: 2019-05-24
Authors: Vishal Lamba; Katrin Sangkuhl; Kinjal Sanghavi; Alyssa Fish; Russ B Altman; Teri E Klein Journal: Pharmacogenet Genomics Date: 2014-01 Impact factor: 2.089
Authors: Jesus Ruiz; María José Herrero; Virginia Bosó; Juan Eduardo Megías; David Hervás; Jose Luis Poveda; Juan Escrivá; Amparo Pastor; Amparo Solé; Salvador Francisco Aliño Journal: Int J Mol Sci Date: 2015-08-25 Impact factor: 5.923