---
title: "GST and TP53 Polymorphisms and Risk of End-Stage Renal Disease"
id: "plos-one-10-impact-of-gst-and-tp53-gene-polymorphisms-on-susceptibility-to-end-stage-renal"
canonical_url: "https://medichelpline.com/clinical-feed/plos-one-10-impact-of-gst-and-tp53-gene-polymorphisms-on-susceptibility-to-end-stage-renal"
content_type: "clinical_feed_article"
specialty: "Nephrology"
source_name: "PLOS ONE (Medicine)"
source_url: "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359809"
published_at: "2026-10-05T14:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# GST and TP53 Polymorphisms and Risk of End-Stage Renal Disease
## Provenance & Clinical Metadata
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- **Specialty:** [Nephrology](https://medichelpline.com/clinical-feed/nephrology.md)
- **Primary Source:** PLOS ONE (Medicine)
- **Source URL:** [Original Journal Publication](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359809)
- **Published At:** 2026-10-05T14:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- End-stage renal disease (**ESRD**) is a final-stage chronic kidney disease with high morbidity and mortality; oxidative stress and gene–environment interactions are implicated in susceptibility. - This case–control study enrolled 305 clinically confirmed ESRD patients and 305 matched healthy controls from District Multan, Punjab, Pakistan, between 30 October 2023 and 28 February 2024. - Genotyping assessed presence/absence of **GSTM1** and **GSTT1** by multiplex PCR and single nucleotide polymorphisms at **GSTP1** (rs1695) and **TP53** (rs1042522) using T-ARMS PCR. - Quality control included internal control amplification (CYP1A1), agarose gel electrophoresis, 10% replicate genotyping with 100% concordance, and negative controls in PCR runs. - Statistical analysis used Chi-square tests for genotype and allele comparisons, Hardy–Weinberg equilibrium, and logistic regression; significance set at P ≤ 0.05. - Key associations observed: GSTM1 null genotype was significantly more frequent among ESRD cases (OR ≈ 2.59); presence of **GSTT1** was more common in cases whereas GSTT1 null was more frequent in controls (OR ≈ 0.69). - At **GSTP1** rs1695, the polymorphic G allele and GG genotype were enriched in ESRD cases; GG genotype conferred a higher risk (reported OR ~4.4) compared with AA. - At **TP53** rs1042522, the polymorphic C allele and CC/CG genotypes were more common in ESRD cases than controls; allelic distributions differed significantly between groups. - Demographic factors: participants aged 26–40 years, males, and smokers were noted to suffer more from ESRD in this cohort. - The authors conclude that genetic variation in the studied **GST** genes and **TP53** rs1042522 may influence ESRD progression in this population. Detailed combined-haplotype effect sizes were not fully reported in the source.
## Clinical Analysis & Structured Key Points
Impact of GST and TP53 gene polymorphisms on susceptibility to end stage renal disease: A case-control analysis | PLOS One Browse Subject Areas ? Click through the PLOS taxonomy to find articles in your field. For more information about PLOS Subject Areas, click here . Article Authors Metrics Comments Media Coverage Reader Comments Figures Figures Abstract Purpose End-stage renal disease (ESRD) is a major global non-communicable condition associated with substantial morbidity and mortality. The current investigation aimed to report the association of GSTM1 , GSTT1 genotypes and single nucleotide polymorphisms (SNPs) in GSTP1 (rs1695) and TP53 (rs1042522) genes with ESRD. Methods Clinically confirmed ESRD patients (n = 305) and healthy controls (n = 305) were enrolled from District Multan in Punjab, Pakistan, during 30-10-2023 till 28-02-2024, following their informed verbal consent. Multiplex and T-ARMS PCR based approaches were used to document the genotype at GSTs and SNPs of targeted genes and their associations with ESRD were analyzed individually as well as in combination. Results A significant association of absence of GSTM1, presence of GSTT1, presence of “G” polymorphic allele at rs1695 in GSTP1, and the presence of “C” polymorphic allele at rs1042522 in TP53 gene was observed with ESRD during the present study. Participants having age ranging between 26–40 years, males and smokers suffered more from ESRD. Conclusion Genetic variations in the studied GSTs, along with rs1695 in GSTP1 and rs1042522 in the TP53 gene, may influence the progression of ESRD. Citation: Mehmood R, Chiang P-C, Rasool M, Asif M, Ghafar A, Khalid M, et al. (2026) Impact of GST and TP53 gene polymorphisms on susceptibility to end stage renal disease: A case-control analysis. PLoS One 21(10): e0359809. https://doi.org/10.1371/journal.pone.0359809 Editor: Mohd Akbar Bhat, Georgetown University Medical Centre, UNITED STATES OF AMERICA Received: August 10, 2025; Accepted: September 15, 2026; Published: October 5, 2026 Copyright: © 2026 Mehmood et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: All relevant data are within the manuscript. Funding: The author(s) received no specific funding for this work. Competing interests: The authors have declared that no competing interests exist. 1. Introduction End-stage renal disease (ESRD) is among the major non-communicable health disorders that have been reported globally and is associated with high rates of morbidity and mortality [ 1 ]. The global burden of chronic kidney disease (CKD) has risen markedly over the past few decades, emerging as a major public health concern. Recent estimates suggested that CKD affects more than 10% of the global population [ 2 ]. The growing prevalence of diabetes mellitus, hypertension, obesity and aging population has substantially increased the number of individuals progressing to ESRD [ 3 ]. The impact of this disease is particularly severe in low and middle income countries, including Pakistan, where delayed diagnosis, limited access to healthcare facilities, and restricted availability of renal replacement therapies further aggravate patient outcomes. Although significant advances have been made in the management of CKD and ESRD, affected individuals continue to experience reduced quality of life, considerable healthcare expenditures, and an elevated risk of cardiovascular complications and premature death [ 4 ]. Disease confirmation is based on a variety of biochemical tests and usually targets the markers for the kidney damage along with glamorous filtration rate (GFR) determination. A CKD is confirmed when the subject has less than 60 mL/min GFR with albumin levels higher than 30 mg/ g of creatinine and having abnormal kidney structure for more than last three months [ 1 ]. It would be worth mentioning that ESRD is the final stage of CKD and participants having GFR less than 15 mL/min are considered as ESRD patients [ 2 ]. If dialysis or kidney transplant is not offered, the situation may become life-threatening [ 3 ]. This abnormal kidney function leads to a variety of drastic consequences including extracellular volume overload, dyslipidemia, anemia along with disturbed mineral and bone [ 4 ]. In ESRD patients, fluid retention has significant contributions towards ventricular dysfunction, hypertension, and cardiovascular abnormalities [ 5 ]. It is the interaction between genes and the environment that decides the likelihood of a subject to develop ESRD. Individuals with family history of this disease are reported to have three to nine time higher risks to develop ESRD [ 6 ]. A USA based investigation has reported that ethnic origin influences the onset and progression of ESRD and African American, Hispanic American and Native American families are known to be at higher risk to develop ESRD [ 7 ]. Consequently, a better understanding of the genetic and environmental factors contributing to disease susceptibility and progression is essential for improving prevention, early diagnosis, and therapeutic interventions. Accumulating evidence suggests that oxidative stress plays a pivotal role in the pathogenesis and progression of ESRD [ 8 ]. Excessive generation of reactive oxygen species (ROS) and impaired antioxidant defenses contribute to inflammation, endothelial dysfunction and progressive renal injury [ 9 ]. Consequently, genetic variations in antioxidant and oxidative stress-related genes have attracted considerable attention as potential determinants of ESRD susceptibility. Nature has blessed us with a variety of chemicals (enzymes, proteins and non-protein) having anti-oxidant potential and among them are the GSTs (Glutathione S-transferases) that are a group of enzymes that plays role in the detoxification of toxic compounds (both endogenous and exogenous) under the oxidative stress conditions [ 10 ]. Humans have seven classes of GSTs and GSTM (mu), GSTT (theta), and GSTP (pi) are most extensively studied as the polymorphisms in these genes are known to result is a variety of pathological conditions [ 11 – 13 ]. Tp53 is a pro-oxidant that contributes to apoptosis following the release of mitochondrial ROS [ 14 ]. p53 proteins regulates the cell replication cycle but under the DNA damage situations, this protein halts the cell cycle until this DNA damage is repaired or upon failure it triggers the cell death preventing the proliferation of the mutated cells [ 15 ]. Presence or absence of GSTT1 and GSTM1 as well as single nucleotide polymorphisms (SNPs) in GSTs and TP53 gene has been linked with CKD and ESRD in various ethnic populations but they have not been explored among the Pakistani population. Hence, this investigation was designed to find out the association of presence or absence of GSTM1 and GSTT1 gene, genotypes at rs1695 in the GSTP1 and rs1042522 in TP53 gene with the ESRD in participants that were enrolled from Multan district in Punjab, Pakistan. 2. Materials and methods 2.1 Participants and sample collection The study design, experimental protocols, and participant handling procedures were reviewed and approved by the Institutional Ethical Review Board (ERB) of Nishtar Medical University, Multan, Pakistan (Approval No. 18186/NMU). All procedures were conducted in accordance with declaration of Helsinki. Informed verbal consent was obtained from all participants prior to enrollment. The ERB approved the use of verbal consent because a substantial proportion of the study population was elderly and had limited literacy. The consent process was documented in the participant data collection forms. For minor participants, consent was obtained from their parents or legal guardians. The required sample size was calculated using the formula N = (Z²P(1 − P)D)/e² as described by Jones et al. [ 16 ], where Z is the standard normal variate corresponding to a 95% confidence level (1.96), P is the expected prevalence, D is the design effect and e is the desired precision. In the absence of reliable local prevalence estimates, P was set at 0.50 to obtain the maximum sample size. The design effect was assumed to be 1.0 and the margin of error was fixed at 5%. Based on these parameters, the minimum required sample size was 384 participants. A total of 610 individuals were ultimately enrolled, exceeding the calculated requirement and providing adequate statistical power for the genetic association analyses. Participant recruitment was conducted between 30 October 2023 and 28 February 2024. Clinically confirmed ESRD patients (n = 305) undergoing dialysis at the Nephrology Department of Nishtar Medical University and Hospital, Multan, were enrolled following informed verbal consent. Epidemiological and clinical information was collected using a standardized questionnaire completed at the time of sampling. ESRD diagnosis was established based on clinical evaluation, laboratory investigations, and imaging findings. Diagnostic tests including the Albumin-to-creatinine ratio (ACR: normal range is G allele (33%)] ( Table 2 ) but the ESRD patients had a significantly higher proportion of polymorphic allele than controls indicating an association of polymorphic allele with the risk to develop ESRD among the enrolled participants during this investigation ( Table 2 ). 3.3 Genotypic and allelic frequency at rs1042522 in TP53 and their association with ESRD When the rs1042522 in TP53 was amplified, a 493 bp amplicon was generated by the outer primers among all participants. While 200 bp and 247 bp fragments from TP53 gene were amplified when homozygous wild (GG) or polymorphic (CC) genotypes were present respectively. Heterozygous genotype (GC) containing participants amplified both 200 and 247 bp products along with 493 bp product generated by the outer primers ( S1 Fig ). Chi-square test analysis revealed that the genotypic frequency at rs1042522 significantly (P C allele (35%)] ( Table 2 ) but the ESRD patients had a higher proportion of polymorphic allele than controls indicating that this allele is potentially associated with the risk of developing ESRD bas
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