Distribution of CYP3A4*1/*1B (rs2740574) and CYP3A5*1/*3 (rs776746) Genetic Variants in Renal Transplant Recipients Treated with Sirolimus in Urmia (Iran).

Abstract

 Introduction. Rapamycin, also referred to as Sirolimus, is an immunosuppressive medication used in kidney transplantation to prevent organ rejection. Sirolimus is metabolized predominantly by the enzymes CYP3A4 and CYP3A5. The objective of this study was to evaluate the distribution of CYP3A4*1/*1B (rs2740574, -392A > G) and CYP3A5*1/*3 (rs776746, 6986A > G) genetic variants in renal transplant recipients treated with Sirolimus in Urmia (Iran). Methods. This assessment involved thirty-nine renal transplant recipients in Urmia Imam Khomeini University Hospital, Urmia (Iran) who were treated with a daily dose of 1mg/day Sirolimus. The CYP3A4*1/*1B and CYP3A5*1/*3 allelic variants were identified using the Restriction Fragment Length Polymorphism-Polymerase Chain Reaction (RFLP-PCR) technique.  Results. The frequencies of CYP3A4 *1/*1 (-392AA), CYP3A4 *1/*1B (-392AG), and CYP3A4 *1B/*1B (-392GG) genotypes and CYP3A4 *1 (-392A) and CYP3A4 *1B (-392G) alleles were 37(94.87%), 2(5.13%), 0(0%), 76(97%), and 2(3%), respectively. The genotypic distribution for CYP3A5 was 0(0%) for CYP3A5*1/*1 (6986AA), 6(15.38%) for CYP3A5*1/*3 (6986AG), and 33(84.62%) for CYP3A5*3/*3 (6986GG). The allelic frequencies were 6(8%) for CYP3A5*1 (6986A) and 72(92%) for CYP3A5*3 (6986G). Only one patient with CYP3A4.