Multigene predictors of tacrolimus exposure in kidney transplant recipients.

Authors :: Pulk RA
Schladt DS
Oetting WS
Guan W
Israni AK
Matas AJ
Remmel RP
Jacobson PA
Source :: Pharmacogenomics [Pharmacogenomics] 2015 Jul; Vol. 16 (8), pp. 841-54. Date of Electronic Publication: 2015 Jun 12.
Publication Year :: 2015
Abstract: Aim: Determine the effect of the genetic variants beyond CYP3A5*3 on tacrolimus disposition.<br />Patients & Methods: We studied genetic correlates of tacrolimus trough concentrations with POR*28, CYP3A4*22 and ABCC2 haplotypes in a large, ethnically diverse kidney transplant cohort (n = 2008).<br />Results: Subjects carrying one or more CYP3A5*1 alleles had lower tacrolimus trough concentrations (p = 9.2 × 10(-75)). The presence of one or two POR*28 alleles was associated with a 4.63% reduction in tacrolimus trough concentrations after adjusting for CYP3A5*1 and clinical factors (p = 0.037). In subset analyses, POR*28 was significant only in CYP3A5*3/*3 carriers (p = 0.03). The CYP3A4*22 variant and the ABBC2 haplotypes were not associated.<br />Conclusion: This study confirmed that CYP3A5*1 was associated with lower tacrolimus trough concentrations. POR*28 was associated with decreased tacrolimus trough concentrations although the effect was small possibly through enhanced CYP3A4 enzyme activity. CYP3A4*22 and ABCC2 haplotypes did not influence tacrolimus trough concentrations. Original submitted 19 December 2014; Revision submitted 2 April 2015.