SUN-296 CYP3A5 AND ABCB1 GENETIC POLYMORPHISMS IN RENAL TRANSPLANT RECIPIENT PATIENTS AND ITS RELATION WITH TACROLIMUS DOSING AND COMPLICATIONS

Abstract

Tacrolimus is the mainstay of immunosuppression in renal transplantation (RT). However, it has highly variable bioavailability and a narrow therapeutic range. Its metabolism depends upon CYP3A4 and ABCB1gene polymorphism. There is limited data regarding the influence of this polymorphisms on TAC drug level and complications from India. This is a prospective study done over a period of 2 years (2016-2018) from NIMS Hyderabad. A total of 152 patients were recruited. Frequency of CYP3AB(A6986>G) & ABCB1 (C1236>T, G2677>T and C3435>T) polymorphisms were detected by PCR followed by Sanger’s sequence-based genotype & RFLP. Accordingly patients were divided into wild variant(CYP3A5-AA) where there is full expression of the enzyme, heterozygous( CYP3A5-AG), homozygous group who were non expressors (CYP3A5-GG). Day 3, 30,60,90 tacrolimus concentrations and tacrolimus concentration/drug (C/D) ratio were measured. Tacrolimus related toxicity, infections and rejections and the serum creatinine at the time of discharge were compared among the groups Out of 152 renal transplant recipients, 120(78%) were males. 37 patients received deceased donor grafts. Immediate graft function was seen in 117(76%). Tacrolimus C/D ratio was less in wild (AA) variety compared to both AG ( 0.006) and GG ( P<o.ooo1). Tacrolimus toxicity was noted in 28(18%) patients, of which ATN 24(85%), TMA 3(11%), Pancreatitis in 1(3.5%). Most common infectious complication was UTI seen in 22(14%) patients (AA-3(10%), AG-9(14%), GG-10 (16.7%) followed by CMV disease. BPAR were seen in 5 patients. ABCB1 polymorphisms and showed no correlation with tacrolimus C/D ratio. Mean serum creatinine at the time of discharge was 1±0.2 in AA, 1.3±0.8 in AG (AA vs AG P < 0.002), 1.27±0.47 in GG(AA vs GG P <0.004). Our study shows that genetic polymorphism effects the tacrolimus dose requirement. Enzyme expressor (AA) is associated with low C/D ratio and higher risk of acute rejection. Heterozygous (AG) and non expressors (GG) are at higher risk of developing tacrolimus related nephrotoxicity and infections. ABCB1 polymorphisms has no significant impact on tacrolimus C/D ratio