Effect of CYP3 A4, CYP3 A5 and ABCB1 gene polymorphisms on the clinical efficacy of tacrolimus in the treatment of nephrotic syndrome.

BACKGROUND: The efficacy of tacrolimus (TAC) is variable in the treatment of nephrotic syndrome (NS), which might be related to genetic variation among patients. Therefore, we aim to investigate the effects of CYP3 A4, CYP3 A5 and ABCB1 gene polymorphisms on the clinical efficacy of TAC in the treatment of NS patients. Methods 100 NS patients were treated with TAC and prednisone and followed up for 3 months. Genotype differences (CYP3 A4*1G, CYP3 A5*3, ABCB1 1236C > T and ABCB1 2677G > T/A) were detected by Sanger sequencing. The clinical efficacy was evaluated by the 24 h urinary protein quantitation, albumin, renal function and the degree of edema. Multivariable logistic regression was used to analyze the effect of gene polymorphisms on the clinical efficacy of TAC.

RESULTS: There were 35 patients (35%) with complete remission, 43 patients (43%) with partial remission, 22 patients (22%) without remission, and no patients with recurrence. For CYP3A4, there were 56, 42, and 2 patients with *1/*1, *1/*1G and *1G/*1G genotype, respectively. For CYP3A5, there were 8, 36 and 56 cases with*1/*1, *1/*3 and *3/*3 genotype, respectively. For ABCB1 C1236T, there were 10, 44, and 46 cases with 1236CC, 1236CT and 1236TT genotype, respectively. For ABCB1 G2677 T/A, there were 13, 57, and 30 patients with 2677GG genotype, 2677GT/GA genotype and 2677TT/AA/TA genotype, respectively. The mutant allele frequencies of CYP3A4*1G, CYP3A5*3, ABCB1 C1236T and ABCB1 G2677 T/A were 23%, 74%, 68% and 58.5%, respectively. Results reveal that the gene polymorphisms of CYP3A4 and CYP3A5 and CCB do not affect the clinical efficacy of TAC. For ABCB1 C1236T,TT genotype can increase the effectiveness 12.085 times compared with CC and CT genotype (P = 0.018, OR = 12.085, 95%CI 1.535-95.148). For ABCB1 G2677 T/A, the clinical efficacy of patients with mutant genotype is 8.683 times than that of wild-type and heterozygous patients (P = 0.042, OR = 8.683, 95%CI 1.080-69.819). Overweight patients can improve the clinical efficacy by 15.838 times (P = 0.020, OR = 15.838, 95%CI1.550-161.788).

CONCLUSIONS: ABCB1 C1236T, ABCB1 G2677 T/A genotype and BMI are probably the factors influencing the clinical efficacy of TAC in treating patients with NS.