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

• Published in: Drugs & therapy perspectives : for rational drug selection and use 2019-07, Vol.35 (7), p.334-340
• Main Authors: Thu, K. Khine, Lwin, Aye Aye, Maw, Khin Than, Htay, Lei Lei, Myint, Khin Mar, Soe, Myat Myat, Linn, Ye Htut, Soe, Chit, Win, Nang Hla Hla
• Format: Article
• Language: English
• Subjects: Arthritis; Breast cancer; Cancer therapies; Chemotherapy; Drug dosages; Enzymes; Genes; Genotype & phenotype; Hospitals; Internal medicine; Leukemia; Lupus; Lymphoma; Medical prognosis; Medicine; Metabolism; Metabolites; Multiple myeloma; Original Research Article; Pharmacotherapy; Pharmacy; Polymorphism; Proteins; Rheumatology
• ISSN: 1172-0360; 1179-1977
• DOI: 10.1007/s40267-019-00631-x

Background 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. Objective 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. Methods 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. Results 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