Epistatic interactions among CYP2C19*2, CYP3A4 and GSTP1 on the cyclophosphamide therapy in lupus nephritis patients

Abstract

Aim: To investigate the impact of genetic variants in CYP2C9, CYP2C19, CYP3A4, GSTT1, GSTM1 and GSTP1 on the efficacy of cyclophosphamide (CYC) therapy in patients with lupus nephritis. Materials and methods: Lupus nephritis patients (n = 220) treated with CYC were included in the study. Results: Logistic regression analysis identified CYP2C19*2 as an independent predictor of CYC therapeutic failure (odds ratio [OR]: 2.69; p = 0.0043). Bivariate and trivariate analysis showed the subjects harboring CYP2C19*2 and GSTP1 (OR: 3.25; p = 0.03), and CYP2C19*2, GSTP1 and CYP3A5*3 have synergistic influence on CYC failure (OR: 8.2; p < 0.0001). Significant decrease in AUC0-t, Cmax and t½ of 4-OH-CYC in patients carrying CYP3A5*3 (p < 0.02). Conclusion: Patients with CYP2C19*2 were at increased risk and CYP2C19*2, CYP3A5*3 and GSTP1 have synergistic influence on CYC failure.