Exploring the role of genetic variants in oxidative stress susceptibility and disease riskAbstract
Oxidative stress, resulting from an imbalance between the production of reactive oxygen species (ROS) and the body's antioxidant defense mechanisms, is implicated in a wide range of physiological and pathological processes. Genetic factors play a significant role in determining an individual's susceptibility to oxidative stress and its associated disorders. This review explores the interplay between oxidative stress and genetics, highlighting the influence of genetic polymorphisms in key antioxidant enzymes and pathways such as superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), and the NRF2-KEAP1 signaling axis—on oxidative stress susceptibility. Additionally, the impact of oxidative stress-related genetic variants on the development and progression of various diseases, including neurodegenerative disorders, cardiovascular diseases, cancer, and metabolic syndromes, is discussed. Understanding the complex relationship between oxidative stress and genetics is essential for elucidating disease mechanisms, identifying potential biomarkers, and developing personalized therapeutic interventions targeting oxidative stress-related pathways.
Keywords:
oxidative stress; genetics; reactive oxygen species (ROS); antioxidant enzymes; disease susceptibility
Resumo
O estresse oxidativo, resultante de um desequilíbrio entre a produção de espécies reativas de oxigênio (EROs) e os mecanismos de defesa antioxidante do organismo, está envolvido em diversos processos fisiológicos e patológicos. Fatores genéticos desempenham um papel significativo na determinação da suscetibilidade de um indivíduo ao estresse oxidativo e aos distúrbios a ele associados. Esta revisão explora a interação entre estresse oxidativo e genética, destacando a influência de polimorfismos genéticos em enzimas e vias antioxidantes essenciais, como superóxido dismutase (SOD), glutationa peroxidase (GPx), catalase (CAT) e o eixo de sinalização NRF2-KEAP1, na suscetibilidade ao estresse oxidativo. Além disso, discute-se o impacto das variantes genéticas relacionadas ao estresse oxidativo no desenvolvimento e na progressão de diversas doenças, incluindo distúrbios neurodegenerativos, doenças cardiovasculares, câncer e síndromes metabólicas. Compreender a complexa relação entre o estresse oxidativo e a genética é essencial para elucidar os mecanismos da doença, identificar potenciais biomarcadores e desenvolver intervenções terapêuticas personalizadas direcionadas às vias relacionadas ao estresse oxidativo.
Palavras-chave:
estresse oxidativo; genética; espécies reativas de oxigênio (EROs); enzimas antioxidantes; suscetibilidade a doenças
1. Introduction
Oxidative stress, a condition defined by an imbalance between the generation of reactive oxygen species (ROS) and the body's antioxidant defenses, has emerged as a central mechanism in both normal physiological functions and a wide range of pathological conditions (Lupu et al., 2024; Houldsworth, 2024). ROS, which include molecules such as superoxide radicals, hydrogen peroxide, and hydroxyl radicals, are naturally produced during cellular metabolism, particularly in processes like mitochondrial respiration and the electron transport chain (Kozlov et al., 2024). Under controlled conditions, these reactive molecules play essential roles in maintaining cellular homeostasis, facilitating signaling pathways, and supporting immune responses (Manoharan et al., 2024). However, when ROS production exceeds the neutralizing capacity of antioxidants, it results in oxidative stress a state that can inflict widespread damage to cellular components, including lipids, proteins, and DNA (Bajaj et al., 2024). This damage undermines the integrity and functionality of cells and tissues, contributing to the development and progression of various diseases (Figure 1).
Schematic representation of oxidative stress mechanisms. This diagram illustrates the imbalance between ROS generation and antioxidant defenses as the central cause of oxidative stress. It highlights how excessive ROS damages cellular components, while moderate levels support normal physiological functions such as signaling and immune response.
The molecular mechanisms underlying oxidative stress involve complex interactions between ROS production, antioxidant systems, and cellular repair processes (Halliwell, 2024). Environmental factors such as air pollution, ultraviolet radiation, industrial toxins, and heavy metals can significantly elevate ROS levels, while lifestyle choices like smoking, excessive alcohol consumption, poor dietary habits, and physical inactivity further exacerbate oxidative stress (Wadgaonkar, 2024). Psychological factors, including chronic stress and sleep deprivation, also contribute by altering hormonal balance and increasing inflammation (Ovsiannikova et al., 2024). Furthermore, genetic predispositions play a critical role, with variations in genes responsible for antioxidant enzyme production and ROS metabolism influencing individual susceptibility to oxidative stress and its associated disorders (Krishnamurthy et al., 2024). This intersection of oxidative stress and genetic variation is increasingly recognized as a key determinant of disease risk, serving as a foundation for personalized approaches in diagnostics and therapy.
This intricate interplay between ROS and antioxidant defenses is implicated in the pathogenesis of numerous chronic diseases (Muscolo et al., 2024), including neurodegenerative disorders, cardiovascular conditions, diabetes, cancer, and respiratory ailments (Muscolo et al., 2024). Emerging research highlights the dual role of ROS, as they are both beneficial in regulated amounts and harmful when overproduced (Vicidomini et al., 2024). This duality underscores the importance of maintaining a delicate balance within cellular systems (Zaher et al., 2024). By understanding the multifaceted nature of oxidative stress and identifying its triggers, researchers and clinicians can develop targeted interventions aimed at mitigating its effects (Dama et al., 2024). Strategies such as antioxidant therapies, lifestyle modifications, and personalized medicine hold promise in addressing oxidative stress-related diseases, emphasizing the need for continued exploration in this dynamic and evolving field (Anwar et al., 2024).
1.1. Causes of oxidative stress
Oxidative stress occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the body's ability to neutralize those using antioxidants (Noel, 2024). This imbalance leads to a cascade of cellular and molecular damage that has wide-ranging effects on health (Mishra et al., 2024). ROS, including superoxide anions, hydrogen peroxide, and hydroxyl radicals, are natural byproducts of normal metabolic processes such as mitochondrial respiration and enzymatic reactions (Vicidomini et al., 2024). Specifically, the electron transport chain, a critical component of energy production, generates ROS during ATP synthesis (Lana et al., 2024). While these reactive molecules are essential for processes like cell signaling and immune defense under controlled conditions, their excessive accumulation overwhelms cellular antioxidant defenses, initiating oxidative damage (Rusciano and Bagnoli, 2024)
Several external and internal factors contribute to the overproduction of ROS and the weakening of antioxidant systems (Li et al., 2024b). Environmental influences are among the primary culprits, with pollutants, ultraviolet (UV) and X-ray radiation, heavy metals, cigarette smoke, and industrial toxins significantly increasing ROS levels in tissues (Shehata et al., 2023). Prolonged exposure to these factors can exacerbate oxidative stress, particularly in vulnerable organs such as the lungs, skin, and liver (Khelfi et al., 2024). Lifestyle choices further amplify this risk; behaviors such as smoking, excessive alcohol consumption, and consuming a diet high in processed foods, refined sugars, and saturated fats, yet deficient in antioxidant-rich fruits and vegetables, greatly strain the body's antioxidant defenses 30. Sedentary lifestyles and physical inactivity also play a critical role in reducing the efficiency of cellular repair mechanisms (Figure 2).
Factors responsible for causing oxidative stress, different environmental factors are responsible for oxidative stress.
Psychological stress represents another significant contributor. Chronic stress disrupts hormonal regulation and activates pathways that promote systemic inflammation, leading to heightened ROS production (Knezevic et al., 2023). Similarly, inflammation caused by infections, autoimmune diseases, or physical injuries stimulates ROS as part of the immune response (Zhang et al., 2023). While ROS generated in this context aim to neutralize pathogens and support healing, excessive production can result in collateral damage to healthy tissues (Lopes et al., 2024).
Antioxidant deficiencies, whether due to poor dietary intake or impaired biosynthesis, exacerbate the inability to counteract oxidative stress (Martemucci et al., 2023b). Key antioxidants such as vitamins C and E, glutathione, and superoxide dismutase (SOD) are integral to neutralizing ROS, and their insufficiency leaves cells vulnerable to oxidative damage (Chaudhary et al., 2023). Additionally, genetic factors can predispose individuals to oxidative stress. Variations in genes encoding antioxidant enzymes or proteins involved in ROS metabolism can alter an individual's capacity to detoxify ROS effectively, thereby increasing susceptibility to oxidative stress and its associated diseases (Jomova et al., 2024).
The combined impact of these factors underscores the multifaceted origins of oxidative stress. It is not only a product of environmental and lifestyle influences but also shaped by intrinsic genetic predispositions and physiological imbalances. These combined factors highlight the multifaceted origins of oxidative stress, underlining its importance in health and disease.
1.2. Diseases associated with oxidative stress
Oxidative stress has been implicated in the development and progression of numerous diseases, spanning various organ systems and physiological processes (Jomova et al., 2023). In neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis (ALS), oxidative stress contributes to neuronal dysfunction and cell death through ROS-induced damage to neurons and insufficient antioxidant defenses (Karvandi et al., 2023). Similarly, cardiovascular diseases, including atherosclerosis, hypertension, myocardial infarction, and heart failure, are influenced by oxidative stress, which drives endothelial dysfunction, lipid peroxidation, inflammation, and vascular remodeling, leading to significant vascular damage (Karvandi et al., 2023).
In cancer, oxidative stress promotes carcinogenesis through mechanisms such as DNA damage, genomic instability, and activation of oncogenic pathways (Dharshini et al., 2023). These processes facilitate tumor growth, angiogenesis, and metastasis, while mutations and altered gene expression caused by ROS exacerbate disease progression (Chen et al., 2024; Yu et al., 2024). Metabolic disorders, including obesity, type 2 diabetes, and metabolic syndrome, are also closely linked to oxidative stress (Martemucci et al., 2023a). Elevated ROS levels impair insulin signaling, disrupt lipid metabolism, and promote inflammation, contributing to insulin resistance and β-cell dysfunction (Ramasubbu and Devi Rajeswari, 2023).
Chronic inflammatory diseases, such as rheumatoid arthritis, inflammatory bowel disease, and asthma, are characterized by heightened oxidative stress and tissue injury (Jomova et al., 2023). ROS produced by immune cells amplify inflammation and exacerbate tissue damage, perpetuating disease severity (Chen et al., 2024). Age-related diseases, including cataracts, osteoporosis, and macular degeneration, are influenced by the cumulative oxidative damage to macromolecules over time (Peng et al., 2024). As antioxidant defenses decline with age, oxidative stress contributes to cellular senescence, tissue dysfunction, and organ degeneration (Maldonado et al., 2023).
Respiratory diseases like chronic obstructive pulmonary disease (COPD), asthma, and acute respiratory distress syndrome (ARDS) are also associated with oxidative stress (Zuo and Wijegunawardana, 2021). Environmental factors, including cigarette smoke and air pollution, as well as inflammation-induced ROS, lead to airway inflammation, epithelial injury, and lung damage. Together, these associations underscore the pervasive role of oxidative stress in the pathogenesis of a wide range of diseases, highlighting its significance in health and therapeutic interventions (Table 1).
2. Literature Review
2.1. Genes associated with oxidative stress
Chronic obstructive pulmonary disease (COPD) and atherosclerosis (AS) are both chronic irreversible diseases in the aged population, with oxidative stress (OS) and immune activation as the pathological basis (Li et al., 2022). Recent studies explored the common hub gene associated with OS and immune cell infiltration in AS and COPD. Genes associated with AS were identified by the differentially expressed genes (DEGs) analysis and weighted gene co-expression network analysis (WGCNA) in the GSE100927 dataset (Quan et al., 2024). Genes associated with COPD were analyzed by WGCNA in the GSE76925 dataset (Wu et al., 2024). The common hub OS-related genes were analyzed by the intersection of the WGCNA modules of AS and COPD and OS-related genes, protein–protein interaction (PPI), and lasso regression (Li et al., 2024b). The diagnostic value of the hub common genes was assessed by receiver operating characteristic analysis (Figure 3 and Table 2).
The association of the hub common genes with immune infiltration in AS and COPD was analyzed by the Spearman correlation method. A total of 455 DEGs (336 upregulated genes and 139 downregulated genes) were identified in GSE100927 (Li et al., 2024a). The turquoise module of WGCNA in GSE100927 and the yellow module of WGCNA in GSE76925, which are the most relevant modules, were intersected and obtained 25 common OS-related genes between AS and COPD (Li et al., 2024a). Those common OS-related genes were enriched in signaling pathways related to immunity and OS. Two hub common OS-related genes (SELL and MMP9) were identified and showed good diagnostic value in AS and COPD. The Spearman correlation analysis showed that the hub common OS-related genes positively or negatively correlated with various infiltrating immune cells. Conclusion Our study identified the common hub genes (SELL and MMP9) associated with OS and immune infiltration in AS and COPD, providing candidate therapeutic targets for AS combined with COPD (Li et al., 2024a).
Neurological disorders include a variety of conditions, including Alzheimer’s disease, motor neuron disease, and Parkinson’s disease, affecting longevity and quality of life, and their pathogenesis is associated with oxidative stress (Houldsworth, 2024). Several of the chronic neurodegenerative pathologies of the CNS share some common features, such as oxidative stress, inflammation, synapse dysfunctions, protein misfolding, and defective autophagia (Perluigi et al., 2024). Neuroinflammation can involve the activation of mast cells, contributing to oxidative stress, in addition to other sources of reactive oxygen species (Conti et al., 2024). Antioxidants can powerfully neutralize reactive oxygen species and free radicals, decreasing oxidative damage (Mohammad et al., 2024). Antioxidant genes, like the manganese superoxide dismutase enzyme, can undergo epigenetic changes that reduce their expression, thus increasing oxidative stress in tissue (Svobodová et al., 2024).
Alternatively, DNA can be altered by free radical damage. The epigenetic landscape of these genes can change antioxidant function and may result in neurodegenerative disease (Houldsworth, 2024). This imbalance of free radical production and antioxidant function increases the reactive oxygen species that cause cell damage in neurons and is often observed as an age-related event (Houldsworth, 2024). Increased antioxidant expression in mice is protective against reactive oxygen species in neurons as is the exogenous supplementation of antioxidants (Houldsworth, 2024). Manganese superoxide dismutase requires manganese for its enzymic function. Antioxidant therapy is considered for age-related neurodegenerative diseases, and a new mimetic of a manganese superoxide dismutase, manganese, is described and suggested as a putative treatment to reduce the oxidative stress that causes neurodegenerative disease (Houldsworth, 2024).
Male fertility can be affected by oxidative stress (OS), which occurs when an imbalance between the production of reactive oxygen species (ROS) and the body’s ability to neutralize them arises (Sengupta et al., 2024). OS can damage cells and influence sperm production. High levels of lipid peroxidation have been linked to reduced sperm motility and decreased fertilization ability (Sengupta et al., 2024). This literature review discusses the most commonly used biomarkers to measure sperm damage caused by ROS, such as the high level of OS in seminal plasma as an indicator of an imbalance in antioxidant activity. The investigated biomarkers include 8-hydroxy-2-deoxyguanosine acid (8-OHdG), a marker of DNA damage caused by ROS, and F2 isoprostanoids (8-isoprostanes) produced by lipid peroxidation.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrotic interstitial pneumonia with a poor prognosis and a pathogenesis that has not been fully elucidated (Mottola et al., 2024). Oxidative stress is closely associated with IPF. It is important to identify reliable diagnostic biomarkers related to oxidative stress through bioinformatics techniques. The gene expression profile data from the GSE70866 dataset was retrieved from the gene expression omnibus (GEO) database (Kong and Chen, 2024). They extracted 437 oxidative stress-related genes (ORGs) from gene set enrichment analysis (GSEA). The GSE141939 dataset was used for single-cell RNA-seq analysis to identify the expression of diagnostic genes in different cell clusters. A total of 10 differentially expressed oxidative stress-related genes (DE-ORGs) were screened. Subsequently, SOD3, CD36, ACOX2, RBM11, CYP1B1, SNCA, and MPO from the 10 DE-ORGs were identified as diagnostic genes based on a random forest algorithm with randomized least absolute shrinkage and selection operator (LASSO) regression. A nomogram was constructed to evaluate the risk of disease. The decision curve analysis (DCA) and clinical impact curves indicated that the nomogram based on these seven biomarkers had extraordinary predictive power. Immune cell infiltration analysis results revealed that DE-ORGs were closely related to various immune cells, especially CYP1B1 was in positive correlation with monocytes and negative correlation with macrophages M1. Single-cell RNA-seq analysis showed that CYP1B1 was mainly associated with macrophages, and SNCA was mainly associated with basal cells. CYP1B1 and SNCA were diagnostic genes associated with oxidative stress in IPF (Kong and Chen, 2024).
Alcohol Use Disorder (AUD) is a persistent condition linked to neuroinflammation, neuronal oxidative stress, and neurodegenerative processes (Tsermpini et al., 2022). While the inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) has demonstrated effectiveness in reducing liver inflammation associated with alcohol, its impact on the brain remains largely unexplored (Bell et al., 2023). A study was conducted to assess the effects of alirocumab, a monoclonal antibody targeting PCSK9 to lower systemic low-density lipoprotein cholesterol (LDL-C), on central nervous system (CNS) pathology in a rat model of chronic alcohol exposure (Wagner et al., 2024). Alirocumab (50 mg/kg) or vehicle was administered weekly for six weeks in 32 male rats subjected to a 35% ethanol liquid diet or a control liquid diet (n = 8 per group). The study evaluated PCSK9 expression, LDL receptor (LDLR) expression, oxidative stress, and neuroinflammatory markers in brain tissues. Chronic ethanol exposure increased PCSK9 expression in the brain, while alirocumab treatment significantly upregulated neuronal LDLR and reduced oxidative stress in neurons and brain vasculature (3-NT, p22phox). Alirocumab also mitigated ethanol-induced microglia recruitment in the cortex and hippocampus (Iba1). Additionally, alirocumab decreased the expression of pro-inflammatory cytokines and chemokines (TNF, CCL2, CXCL3) in whole brain tissue and attenuated the upregulation of adhesion molecules in brain vasculature (ICAM1, VCAM1, eSelectin) (Wagner et al., 2024). The study presents novel evidence that alirocumab diminishes oxidative stress and modifies neuroimmune interactions in the brain elicited by chronic ethanol exposure. Further investigation is needed to elucidate the mechanisms by which PCSK9 signaling influences the brain in the context of chronic ethanol exposure (Wagner et al., 2024).
The incidence of chronic kidney disease (CKD) has been increasing in recent years, gradually becoming a global health crisis. Due to limited treatment options, novel molecular pathways are urgently required to advance the treatment and diagnosis of CKD (Lv and Zhang, 2019). The characteristics of differentially expressed genes (DEGs) in CKD patients were analyzed using Gene Expression Omnibus (GEO) database, and genes related to oxidative stress were retrieved from the Genecard database (Bai et al., 2024). Subsequently, a comprehensive approach was applied, including immune infiltration analysis, weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis, to identify hub genes among differentially expressed immune-related oxidative stress genes (DEIOSGs) (Bai et al., 2024). Validation of hub genes was performed using an external data set, and diagnostic potential capability was evaluated through receiver operating curve (ROC) analysis. In animal experiments, the expression of hub genes in CKD was confirmed by inducing a CKD model through a 5/6 nephrectomy procedure. Finally, the relationship between these hub genes and clinical characteristics were assessed using the Nephroseq v5 database. 29 DEIOSGs were identified by comprehensive bioinformatics analysis. PPI analysis screened the hub genes NCF2, S100A9, and SELL. ROC analysis demonstrated excellent diagnostic efficacy. Further validation from other databases and animal experiments confirmed a substantial upregulation in the expression of hub genes in CKD (Figure 3). Additionally, clinical correlation analysis established a clear link between hub gene expression and renal function deterioration (Bai et al., 2024).
Worldwide prevalence of diabetes mellitus motivates a number of association studies to be conducted throughout the world (Chen et al., 2012). Eleven polymorphisms from nine candidate genes in oxidative stress pathway have been analyzed in eastern Indian type 2 diabetic patients (n = 145) and healthy controls (n = 100) (Tonin et al., 2024). Different biochemical parameters were also analyzed for their association with the disease. Significant associations were observed for rs2070424 A>G SOD1 (OR 3.91, 95% CI 2.265–8.142, P < 0.001), rs854573 A>G PON1 (OR 3.415, 95% CI 2.116–5.512, P < 0.001), rs6954345 G>C PON2 (OR 3.208, 95% CI 2.071–4.969, P < 0.001), RAGE rs1800624 −374 T>A (OR 3.58, 95% CI 2.218–5.766, P < 0.001), and NOS3 −786 T>C (OR 3.75, 95% CI 2.225–6.666, P < 0.001) (Gallegos-Arreola et al., 2024). Haplotype containing two risk alleles of PON1 and PON2 genes was significantly associated with disease (OR 8.34, 95% CI 1.554–44.804, P < 0.002). The results suggest that carriers of major and efficient alleles of oxidative stress genes are more likely to survive the comorbid complications and single copy of risk allele is sufficient for developing the disease (Gallegos-Arreola et al., 2024) (Figure 3).
Heart failure results from various known cardiovascular diseases, such as coronary artery disease, or can be the result of an idiopathic dilated cardiomyopathy (Xu et al., 2024). It is of utmost importance for diagnostic, preventive, and therapeutic purposes to understand the cellular events that trigger the cascade of functional and structural changes that result in the development and progression of heart failure (Xu et al., 2024). Progress in unraveling the genetic background in both ischemic and nonischemic cardiomyopathies has been slow compared with that for monogenic diseases, such as some forms of hypertrophic cardiomyopathy or familial dilated cardiomyopathies (Xu et al., 2024). Susceptibility to and risk of progression of heart failure are likely both influenced by many genes acting in concert or independently. Among the diverse Subcellular mechanisms implicated in the pathogenesis and progression of heart failure, reactive oxygen species play a major role. The search for genetic polymorphisms in clinical association studies in order to identify genotypes susceptible to develop and affect the progression to heart failure has been the focus of many investigations over the past several years (Xu et al., 2024). In this review, the authors summarize the current data in support of the role of various polymorphisms of genes related to oxidative stress in the susceptibility to develop heart failure, and its progression.
The paraoxons (PON) gene cluster contains at least three members, including PON1, PON2, and PON3, located on chromosome 7q21.3–22.1 (Jakubowski, 2024). Until now there has been little insight into the role of the respective gene products in human physiology and pathology. However, emerging evidence from biochemical and genetic experiments is providing clues about the role(s) of the products of these genes, which indicates that PON(s) acts as important guardians against cellular damage from toxic agents, such as organophosphates, oxidized lipids in the plasma low-density lipoproteins (Jakubowski, 2024). In parallel, substantial data have been published on the association between the polymorphisms of PON(s) and coronary heart disease (Chatzopoulou et al., 2024). It has become clear that the polymorphisms significantly affect the prevalence of coronary heart disease. However, the associations between the PON(s) polymorphisms and most of these conditions were found to be inconsistent when additional populations were investigated. This contribution provides an overview of the status of research of each of the three genes and the available association studies and the potential problems in interpreting the data.
3. Future Prospects
As the study of genetic variants influencing oxidative stress susceptibility continues to evolve, several promising directions warrant further exploration. Large-scale studies across multi-ethnic populations are essential for identifying population-specific genetic biomarkers associated with oxidative stress-related diseases. Such efforts will support the advancement of precision medicine by tailoring interventions based on genetic diversity. The integration of multi-omics technologies including genomics, transcriptomics, proteomics, metabolomics, and epigenomics offers powerful tools to unravel the complex regulatory networks governing oxidative stress. Leveraging artificial intelligence (AI) and machine learning (ML) for the analysis of high-dimensional omics data can facilitate the discovery of novel gene-environment interactions, regulatory pathways, and predictive biomarkers for disease susceptibility and progression.
CRISPR-Cas9-based gene editing holds significant promise for correcting or modulating pathogenic genetic variants in oxidative stress-related pathways. In particular, CRISPR interference (CRISPRi) and activation (CRISPRa) systems can be employed to fine-tune gene expression levels of antioxidant enzymes or ROS-generating factors. Furthermore, RNA-based therapeutics, including small interfering RNAs (siRNAs) and antisense oligonucleotides, are emerging as targeted approaches to modulate oxidative stress at the post-transcriptional level.
Understanding the interplay between genetic predispositions, epigenetic modifications, and environmental exposures will be critical for deciphering the multifactorial nature of oxidative stress-related diseases. Longitudinal cohort studies tracking oxidative stress biomarkers (OSBs), gene expression, and lifestyle factors over time can offer valuable insights into disease development and prognosis. In summary, advances in gene editing, computational biology, and systems medicine will continue to reshape our understanding of oxidative stress and its genetic underpinnings. These innovations may ultimately enable the development of personalized preventive strategies and targeted therapies, significantly improving clinical outcomes and quality of life.
4. Conclusion
Oxidative stress refers to a state in which the total production of reactive oxygen species (ROS) exceeds the capacity of the cellular antioxidant system to neutralize their damaging effects, contributing to the onset and progression of numerous diseases. Understanding the genetic basis of oxidative stress provides valuable insights into individual disease susceptibility and offers new avenues for targeted therapeutic interventions. This review has highlighted recent advances in identifying genetic variants within oxidative stress response pathways (OSRPs), including key genes such as SOD, GPx, CAT, NRF2, and KEAP1, and their associations with complex diseases like cardiovascular disorders, neurodegenerative conditions, metabolic syndromes, and cancer. It also emphasized the importance of genome-wide association studies (GWAS), functional genomics, and systems biology in mapping these associations. Importantly, this knowledge has significant translational potential. Identifying genetic biomarkers of oxidative stress may aid in early diagnosis, risk stratification, and personalized treatment planning. Furthermore, it opens the door for the development of targeted therapies, such as antioxidant supplementation tailored to an individual’s genetic profile or gene-editing approaches to correct dysfunctional oxidative stress pathways. In summary, bridging the gap between genetic research and clinical practice can help transform our approach to managing oxidative stress-related diseases—enabling more precise, predictive, and preventive healthcare.
Acknowledgements
The authors are thankful to Ala-too International University Bishkek Kyrgyzstan, Sks Hospital Medical College and Research Center, Mathura, India, Ras Al Khaimah College of Medical Sciences, RAK Medical, and Health Sciences University, Ras al Khaimah, UAE. P.O. College of Medicine, Ajman University, Ajman, UAE, and Al-Azhar University, Cairo, Egypt for financial support.
Data Availability Statement
We confirm that the data supporting the findings of the study will be shared upon reasonable request.
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Editor:
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