Department of Biochemistry, Center for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, 625 021, Tamil Nadu, India.
Center for Molecular and Translational Medicine, Georgia State University, 157 Decatur Street SE, Atlanta, GA, 30303, USA.
Mol Cell Biochem. 2020 Jun;469(1-2):21-28. doi: 10.1007/s11010-020-03724-8. Epub 2020 Apr 18.
Chronic kidney disease (CKD) is one of the main causes of early death in humans worldwide. Glutathione S-Transferases (GSTs) are involved in a series of xenobiotics metabolism and free radical scavenging. The previous studies elucidated the interlink between GST variants and to the development of various diseases. The present case-control study performed to ascertain whether GST polymorphisms are associated with the incidence and advancement of CKD. From the Southern part of India, a total of 392 CKD patients (nondialysis, ND; n = 170, end-stage renal disease, ESRD; n = 222) and 202 healthy individuals were enrolled. Patients were followed-up for 70 months. Serum biochemical parameters were recorded, and the extraction of DNA was done from the patient's blood samples. To genotype study participants, multiplex PCR for GSTM1/T1 was performed. Statistical analysis was carried out to analyze the relationship between gene frequency and sonographic grading, as well as biochemical parameters for disease development. The GSTM1-null genotype showed threefold increased risk (OR = 2.9304; 95% CI 1.8959 to 4.5296; P < 0.0001) to CKD development and twofold increased risk (OR = 1.8379; 95% CI 1.1937 to 2.8299; P = 0.0057) to ESRD progression. During the mean follow-up of 41 months study, multivariate Cox regression analysis revealed that GSTM1-null genotype has 4 times increased the risk for all-cause rapid disease progression to ESRD among ND patients and 3.85-fold increased risk for death among ESRD patients. Survival analysis revealed that patients with GSTM1-present allele showed a significantly diminished risk of mortality compared to patients bearing the GSTM1-null allele among ESRD patients with a hazard ratio of 4.6242 (P < 0.0001). Thus, present data confirm that GSTM1-null genotype increased the risk for all-cause rapid disease progression to ESRD among ND patients. Based on our results, GSTM1-null genotype could be considered as a significant predictor for causing mortality among CKD patients when compared to all other variables.
慢性肾脏病 (CKD) 是全球人类早逝的主要原因之一。谷胱甘肽 S-转移酶 (GSTs) 参与一系列外源性物质代谢和自由基清除。先前的研究阐明了 GST 变体与各种疾病发展之间的联系。本病例对照研究旨在确定 GST 多态性是否与 CKD 的发生和进展有关。从印度南部，共纳入 392 名 CKD 患者（非透析，ND；n=170，终末期肾病，ESRD；n=222）和 202 名健康个体。对患者进行了 70 个月的随访。记录血清生化参数，并从患者的血液样本中提取 DNA。对研究参与者进行多重 PCR 检测 GSTM1/T1 基因型。进行统计分析以分析基因频率与超声分级以及疾病发展的生化参数之间的关系。GSTM1 缺失基因型使 CKD 发展的风险增加三倍（OR=2.9304；95%CI 1.8959 至 4.5296；P<0.0001），ESRD 进展的风险增加两倍（OR=1.8379；95%CI 1.1937 至 2.8299；P=0.0057）。在平均 41 个月的研究随访期间，多变量 Cox 回归分析显示，GSTM1 缺失基因型使 ND 患者全因快速疾病进展至 ESRD 的风险增加 4 倍，ESRD 患者死亡的风险增加 3.85 倍。生存分析显示，与携带 GSTM1 缺失等位基因的患者相比，携带 GSTM1 存在等位基因的 ESRD 患者的死亡率显著降低，风险比为 4.6242（P<0.0001）。因此，现有数据证实，GSTM1 缺失基因型使 ND 患者全因快速疾病进展至 ESRD 的风险增加。基于我们的结果，与所有其他变量相比，GSTM1 缺失基因型可被视为 CKD 患者死亡的重要预测因子。
