Indrawijaya Yen Ya, Artarini Aluicia A, Hamijoyo Laniyati, Iwo Maria I
Doctoral Program, School of Pharmacy, Institut Teknologi Bandung, Bandung, Indonesia.
Department of Pharmacy, Faculty of Medicine and Health Sciences, Universitas Islam Negeri Maulana Malik Ibrahim, Malang, Indonesia.
Narra J. 2024 Dec;4(3):e1144. doi: 10.52225/narra.v4i3.1144. Epub 2024 Nov 15.
Glutathione-S-transferase alpha-1 () is an enzyme with high conjugation activity against aldophosphamide, a metabolite of cyclophosphamide and promoter polymorphisms in may influence the cyclophosphamide effectiveness. The aim of this study was to evaluate the effectiveness and side effects of cyclophosphamide in lupus nephritis patients, using variants as predictors. A case-control study was conducted at Hasan Sadikin Hospital, Bandung, Indonesia, involving 100 lupus nephritis patients from February 2023 to January 2024. The PCR-Sanger sequencing was used to genotype five selected single nucleotide polymorphisms (SNPs) in the promoter: - 52 A > G, -69 T > C, -513 A > G, -567 G > T, and -631 G > T. The endpoint was assessed after six doses of cyclophosphamide by evaluating renal function, disease activity and side effects. Results indicated that six doses of intravenous cyclophosphamide treatment improved renal function and disease activity in the patients, as evidenced by significant changes in serum creatinine (0.79 vs 0.69 mg/dL), dipstick proteinuria (3.00 vs 1.50), creatinine clearance (98.50 vs 109.50 mL/min), and Modified Systemic Lupus Erythematosus Disease Activity Index 2000 (M-SLEDAI-2 K) score (8.61 vs 6.95). The AG genotype at - 513 A > G was associated with reduced cyclophosphamide effectiveness (odds ratio (OR): 0.19; 95%CI: 0.19-0.60; = 0.019). The GT genotype at -631 G > T independently increased the progression of anemia (OR: 2.41; 95%CI: 0.26-22.12; = 0.040). This study highlights that the presence of variants affected cyclophosphamide effectiveness in lupus nephritis patients, with heterozygous polymorphisms at -513 (AA to AG) and -631 (TT to GT) predicting reduced effectiveness of cyclophosphamide by enhancing promoter activity, while anemia further exacerbated lupus nephritis disease severity. polymorphism was not associated with the presence of alopecia, amenorrhea, gastrointestinal disorders, and leukopenia during cyclophosphamide therapy.
谷胱甘肽 - S - 转移酶α - 1（）是一种对环磷酰胺的代谢产物醛磷酰胺具有高结合活性的酶，而该基因中的启动子多态性可能会影响环磷酰胺的疗效。本研究旨在以该基因变体作为预测指标，评估环磷酰胺在狼疮性肾炎患者中的疗效及副作用。2023年2月至2024年1月，在印度尼西亚万隆的哈桑·萨迪金医院进行了一项病例对照研究，纳入了100例狼疮性肾炎患者。采用聚合酶链反应 - 桑格测序法对该基因启动子中五个选定的单核苷酸多态性（SNP）进行基因分型：-52 A＞G、-69 T＞C、-513 A＞G、-567 G＞T和-631 G＞T。在给予六剂环磷酰胺后，通过评估肾功能、疾病活动度和副作用来评估研究终点。结果表明，六剂静脉注射环磷酰胺治疗改善了患者的肾功能和疾病活动度，血清肌酐（0.79 vs 0.69 mg/dL）、尿蛋白试纸检测结果（3.00 vs 1.50）、肌酐清除率（98.50 vs 109.50 mL/min）以及2000年改良系统性红斑狼疮疾病活动指数（M - SLEDAI - 2K）评分（8.61 vs 6.95）的显著变化证明了这一点。-513 A＞G位点的AG基因型与环磷酰胺疗效降低相关（比值比（OR）：0.19；95%置信区间：0.19 - 0.60；P = 0.019）。-631 G＞T位点的GT基因型独立增加了贫血的进展（OR：2.41；95%置信区间：0.26 - 22.12；P = 0.040）。本研究强调，该基因变体的存在影响了狼疮性肾炎患者中环磷酰胺的疗效，-513（AA至AG）和-631（TT至GT）位点的杂合多态性通过增强该基因启动子活性预测环磷酰胺疗效降低，而贫血进一步加剧了狼疮性肾炎疾病的严重程度。该基因多态性与环磷酰胺治疗期间脱发、闭经、胃肠道疾病和白细胞减少的存在无关。
