Influence of Multidrug Resistance 1 Gene Variants on Response to Intravenous Methylprednisolone Pulse in Systemic Lupus Erythematosus Patients: Preliminary Results.

Abstract

Introduction/objectives: Genetic variations could explain individual responses to drugs. This case-control study aimed to investigate the association between the multidrug resistance 1 (MDR1) gene exonic single nucleotide variants (SNVs), rs1128503/C1236T and rs1045642/C3435T, and the response to intravenous methylprednisolone in Egyptian patients with active systemic lupus erythematosus (SLE).

Method: Real-time polymerase chain reaction was used. Patients were divided into responders and resistant based on the SLE Disease Activity Index (SLEDAI). The degree of improvement was determined according to a 7-point Likert scale.

Results: The study included 80 patients: 40 patients with renal flares and 40 patients with extrarenal flares. In patients with extrarenal flares, 71.4% of responders had the CT+TT model of the C1236T variant versus 36.8% of resistant patients (p = 0.028); the T allele was detected in 47.6% of responders versus 23.7% of resistant patients (p = 0.026). Patients with the TT and CT genotypes, TT+CT model, and T allele of the C1236T variant had significant improvement based on the Likert scale compared with the CC genotype, CC model and C allele (p = 0.049, 0.038, 0.010 and <0.001, respectively). In the renal subgroup, patients with the CC genotype and C allele of the C3435T variant had significant improvement based on the Likert scale compared with the CT genotype and T allele (p = 0.028 and 0.046, respectively). Patients with the CC model had significantly lower post-treatment proteinuria compared with the TT+CT model (p = 0.024).

Conclusion: MDR1 C1236T variant allele and C3435T wild allele seem to enhance the response to glucocorticoids in Egyptian patients with active SLE.