Effect of GSTP1 polymorphism on efficacy and safety of cyclophosphamide aggressive therapy in lupus nephropathy patients

Abstract

Lupus nephritis (LN) occurs in up to 60% of adults with systemic lupus erythematosus (SLE) and is a predictor of poor survival. Cyclophosphamide (CYC) is regarded as the most effective immunosuppressive medication to improve survival for patients with LN. This prospective hospital-based study was conducted to identify the effect of glutathione S transferase Pi-1 (GSTP1) genotypes on the efficacy and safety of CYC aggressive therapy. We enrolled SLE nephropathy patients admitted to the Department of Rheumatology of the 500-bed Yangon Specialty Hospital (YSH), Yangon, Myanmar, who received CYC aggressive therapy for 6 months according to treatment guidelines for SLE patients with renal involvement. The frequencies of I/I, I/V and V/V GSTP1 genotypes were determined using the polymerase chain reaction-restriction fragment length polymorphism method. The efficacy of CYC aggressive therapy between LN patients with wild GSTP1 (I/I) and those with polymorphic GSTP1 (I/V or V/V) genotypes was evaluated by comparing 24-h urinary protein levels and assessing the remission rates at 3 and 6 months after initiation of CYC. CYC-related myelotoxicity was assessed by reviewing complete blood picture results on the 10th day after CYC treatment. In total, 95 eligible patients were recruited. The frequencies of I/I, I/V and V/V GSTP1 genotypes were 54.7, 41.1 and 4.2%, respectively. At 3 and 6 months after CYC treatment, mean 24-h urinary protein had significantly decreased from baseline in both wild and polymorphic genotype groups (p < 0.001). No significant differences were seen between the wild and polymorphic genotype groups with regard to changes in 24-h urinary protein levels, remission at 3 and 6 months or myelotoxicity. CYC aggressive therapy had similar efficacy and caused no significant differences in myelotoxicity in wild GSTP1 (I/I) and polymorphic GSTP1 (I/V or V/V) genotypes in patients treated according to YSH guidelines for SLE patients with renal involvement.