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GSTM1-null allele predicts rapid disease progression in nondialysis patients and mortality among South Indian ESRD patients

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Abstract

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.

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Acknowledgements

The research presented in this article was supported by the University Grants Commission (UGC), New Delhi, India, through CEGS, CAS,and UPE schemes. V. Vasudevan thanks UGC for the award of Genomics-Meritorious Research Fellowships.

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Authors and Affiliations

  1. Department of Biochemistry, Center for Excellence in Genomic Sciences, School of Biological Sciences, Madurai Kamaraj University, Madurai, 625 021, Tamil Nadu, India

    Varadaraj Vasudevan, Tharmarajan Ramprasath, Krishnaswamy Sampathkumar, Shanavas Syed Mohamed Puhari, Subramani Yuvaraj & Govindan Sadasivam Selvam

  2. Center for Molecular and Translational Medicine, Georgia State University, 157 Decatur Street SE, Atlanta, GA, 30303, USA

    Tharmarajan Ramprasath & Krishnaswamy Sampathkumar

  3. Department of Nephrology, Meenakshi Mission Hospital and Research Centre, Lake View, Melur Road, Madurai, India

    Krishnaswamy Sampathkumar

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  1. Varadaraj Vasudevan
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  3. Krishnaswamy Sampathkumar
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Conceptualization—VV, TR, GSS; Methodology and Sample collection—KS, VV; Formal analysis—VV. Investigation—VV, TR, GSS, SSMP, and SY; Writing—Original draft—VV, TR; Review and Editing—VV, TR, and GSS; Funding acquisition—GSS.

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Correspondence to Govindan Sadasivam Selvam.

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Vasudevan, V., Ramprasath, T., Sampathkumar, K. et al. GSTM1-null allele predicts rapid disease progression in nondialysis patients and mortality among South Indian ESRD patients. Mol Cell Biochem 469, 21–28 (2020). https://doi.org/10.1007/s11010-020-03724-8

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