William S Oetting1, Casey Dorr2,3, Rory P Remmel4, Arthur J Matas5, Ajay K Israni2,3, Pamala A Jacobson1. 1. Department of Experimental and Clinical Pharmacology, University of Minnesota, Minneapolis, MN. 2. Minneapolis Medical Research Foundation, Minneapolis, MN. 3. Department of Medicine, Hennepin County Medical Center, University of Minnesota, Minneapolis, MN. 4. Department of Medicinal Chemistry, University of Minnesota, Minneapolis, MN. 5. Department of Surgery, University of Minnesota, Minneapolis, MN.
Abstract
PURPOSE OF REVIEW: Identification of genetic variants to aid in individualized treatment of solid organ allograft recipients would improve graft survival. We will review the current state of knowledge for associations of variants with transplant outcomes. RECENT FINDINGS: Many studies have yet to exhibit robust and reproducible results, however, pharmacogenomic studies focusing on cytochrome P450 (CYP) enzymes, transporters and HLA variants have shown strong associations with outcomes and have relevance towards drugs used in transplant. Genome wide association study data for the immunosuppressant tacrolimus have identified multiple variants in the CYP3A5 gene associated with trough concentrations. Additionally, APOL1 variants had been shown to confer risk to the development of end stage renal disease in African Americans. SUMMARY: The field is rapidly evolving and new technology such as next generation sequencing, along with larger cohorts, will soon be commonly applied in transplantation to understand genetic association with outcomes and personalized medicine.
PURPOSE OF REVIEW: Identification of genetic variants to aid in individualized treatment of solid organ allograft recipients would improve graft survival. We will review the current state of knowledge for associations of variants with transplant outcomes. RECENT FINDINGS: Many studies have yet to exhibit robust and reproducible results, however, pharmacogenomic studies focusing on cytochrome P450 (CYP) enzymes, transporters and HLA variants have shown strong associations with outcomes and have relevance towards drugs used in transplant. Genome wide association study data for the immunosuppressant tacrolimus have identified multiple variants in the CYP3A5 gene associated with trough concentrations. Additionally, APOL1 variants had been shown to confer risk to the development of end stage renal disease in African Americans. SUMMARY: The field is rapidly evolving and new technology such as next generation sequencing, along with larger cohorts, will soon be commonly applied in transplantation to understand genetic association with outcomes and personalized medicine.
Authors: Chaitali Passey; Angela K Birnbaum; Richard C Brundage; William S Oetting; Ajay K Israni; Pamala A Jacobson Journal: Br J Clin Pharmacol Date: 2011-12 Impact factor: 4.335
Authors: H K Pihlstrøm; G Mjøen; S Mucha; G Haraldsen; A Franke; A Jardine; B Fellström; H Holdaas; E Melum Journal: Am J Transplant Date: 2016-09-19 Impact factor: 8.086
Authors: Lennaert C P Borra; Joke I Roodnat; Judith A Kal; Ron A A Mathot; Willem Weimar; Teun van Gelder Journal: Nephrol Dial Transplant Date: 2010-02-26 Impact factor: 5.992
Authors: Agnieszka A Prytula; Antonia H Bouts; Ron A A Mathot; Teun van Gelder; Ludwig K Croes; Wim Hop; Karlien Cransberg Journal: Pediatr Transplant Date: 2012-06-13
Authors: K E Caudle; A E Rettie; M Whirl-Carrillo; L H Smith; S Mintzer; M T M Lee; T E Klein; J T Callaghan Journal: Clin Pharmacol Ther Date: 2014-08-06 Impact factor: 6.875
Authors: S A Scott; K Sangkuhl; C M Stein; J-S Hulot; J L Mega; D M Roden; T E Klein; M S Sabatine; J A Johnson; A R Shuldiner Journal: Clin Pharmacol Ther Date: 2013-05-22 Impact factor: 6.875
Authors: William S Oetting; Baolin Wu; David P Schladt; Weihua Guan; Jessica van Setten; Brendan J Keating; David Iklé; Rory P Remmel; Casey R Dorr; Roslyn B Mannon; Arthur J Matas; Ajay K Israni; Pamala A Jacobson Journal: Transplantation Date: 2019-06 Impact factor: 4.939