- All Journals
- Al-Qadisiyah University
- Basrah University
- Kirkuk University
- Mosul University
- The Iraqi Borad for Medical Specialization
- University of Anbar
- University of Technology
- Al Mustafa University
- Al-Zahraa University for Women
- Alnoor University
- Kunooz University
- Misan University
- Ninevah University
- Tikrit University
- University of Al-Hamdaniya
- University of Kerbala
Structural and Functional Analysis of DNA-repair Gene Variants (XRCC1, ERCC2/XPD) and their Relevance to Chronic Kidney Disease Pathogenesis | ||
| Al- Anbar Medical Journal | ||
| Volume 22, Issue 3, July 2026, Pages 143-151 PDF (5.7 M) | ||
| Document Type: Original articles | ||
| DOI: 10.33091/amj.2026.166477.2498 | ||
| Authors | ||
| Fahad D. F. Abo-Ghneim* 1; Dhafer A. F. Al-Koofee2; Hussain Jassim Mohammed3 | ||
| 1Department of Medical Laboratory, Faculty of Health and Medical Techniques, Al-Furat Al-Awsat Technical University, Najaf, Iraq. | ||
| 2Department of Clinical Laboratory Science, Faculty of Pharmacy, University of Kufa, Najaf, Iraq. | ||
| 3Department of Chemistry, Faculty of Science, University of Kufa, Najaf, Iraq. | ||
| Abstract | ||
| Background: According to statistics, chronic kidney disease (CKD) is the fourth leading cause of death in the world and its rate of 4.32% of total deaths in Iraq. Over the past few years, several single -nucleotide polymorphisms (SNPs) have been recognized to be associated with increased risk for CKD. Objectives: To computationally evaluate the impact of nonsynonymous single-nucleotide polymorphisms (nsSNPs) in the coding regions of the XRCC1 and XPD genes using multiple predictive tools. Materials and Methods: Several prediction methods and in silico theoretical models were used to examine non-synonymous SNPs in the XRCC1 and XPD genes. It has been demonstrated that the structure and function of the XRCC1 and XPD proteins, which are involved in deoxyribonucleic acid (DNA) repair, are affected by potentially harmful mutations rs25487, rs1799782, rs13181, and rs1799793. Results: High-confidence three-dimensional structures of the human XRCC1 and XPD proteins were produced using the SWISS-MODEL platform. Mutant models with missense variations (rs25487, rs1799782, rs13181, and rs1799793) exhibited striking changes in protein stability and structure. Several variations have been shown to negatively impact protein function by in silico prediction techniques (i-Mutant, PolyPhen-2, PROVEAN, and SNPs and GO), with rs1799793 exhibiting the highest correlation with illness. The discussed polymorphisms appear to be highly relevant to DNA repair and genomic stability, a conclusion supported by additional analysis of protein–protein interactions, evolutionary conservation within and outside the species, as well as protein classification. Conclusion: Our conclusion was that the rs1799793 variant impacted on the CKD. While the rs13181 polymorphism has shown protein stability increases, the others, including rs25487 and rs1799782 have shown decreases in their stability. Prediction tools (i-Mutant, PolyPhen-2, PROVEAN and SNPs&GO) indicated that XPD variants were generally benign, while the impact of XRCC1 variants could be deleterious. | ||
| Keywords | ||
| XRCC1; XPD; Nonsynonymous SNPs; SNP effect; Protein stability | ||
| References | ||
|
[1] A. Francis et al., "Chronic kidney disease and the global public health agenda: an international consensus," Nature Reviews Nephrology, vol. 20, no. 7, pp. 473-485, 2024. [2] J. Shan, Z. Cao, and S. Yu, "Advances in understanding diabetic kidney disease progression and the mechanisms of acupuncture intervention," International Journal of General Medicine, 17: pp. 5593-5609, 2024. [3] D. Banerjee et al., "Management of hypertension and renin-angiotensin-aldosterone system blockade in adults with diabetic kidney disease: Association of British Clinical Diabetologists and the Renal Association UK guideline update 2021," BMC nephrology, vol. 23, no. 1, p. 9, 2022. [4] Y. Ostchega, C. D. Fryar, T. Nwankwo, and D. T. Nguyen, "Hypertension prevalence among adults aged 18 and over: United States, 2017–2018," (364):1-8, 2020. [5] D. Gohil, A. H. Sarker, and R. Roy, "Base excision repair: mechanisms and impact in biology, disease, and medicine," International journal of molecular sciences, vol. 24, no. 18, p. 14186, 2023. [6] H. Wang, M. Guo, H. Wei, and Y. Chen, "Targeting p53 pathways: mechanisms, structures and advances in therapy," Signal transduction and targeted therapy, vol. 8, no. 1, p. 92, 2023. [7] Y.-Y. Gu, X.-S. Liu, X.-R. Huang, X.-Q. Yu, and H.-Y. Lan, "Diverse role of TGF-β in kidney disease," Frontiers in cell and developmental biology, vol. 8, p. 123, 2020. [8] Q. Hong, H. Kim, G.-Y. Cai, X.-M. Chen, J. C. He, and K. Lee, "Modulation of TGF-β signaling new approaches toward kidney disease and fibrosis therapy," International journal of biological sciences, vol. 21, no. 4, p. 1649, 2025. [9] M. A. Tejasvi, G. Maragathavalli, P. U. Kumar, M. Ramakrishna, V. Raghavan, and A. A. Ck, "Impact of ERCC2 gene polymorphisms on OSCC susceptibility and clinical characteristics," Global Medical Genetics, vol. 7, no. 04, pp. 121-127, 2020. [10] W. Zeng, W. Xu, and W. Long, "The association between XPD rs13181 and rs1799793 polymorphism and oral cancer risk: evidence from a meta-analysis," BMC cancer, vol. 24, no. 1, p. 738, 2024. [11] A. K. Mitra, N. Singh, V. K. Garg, R. Chaturvedi, M. Sharma, and S. K. Rath, "Statistically significant association of the single nucleotide polymorphism (SNP) rs13181 (ERCC2) with predisposition to Squamous Cell Carcinomas of the Head and Neck (SCCHN) and Breast cancer in the north Indian population," Journal of Experimental & Clinical Cancer Research, vol. 28, no. 1, p. 104, 2009. [12] H. Kobayashi and S. Imanaka, "Understanding the impact of mitochondrial DNA mutations on aging and carcinogenesis," International Journal of Molecular Medicine, vol. 56, no. 2, p. 118, 2025. [13] A. Sarasin, "The French cohort of DNA repair-deficient xeroderma pigmentosum patients: risk of hematological malignancies," Cancers, vol. 15, no. 10, p. 2706, 2023. [14] H. Bencharef et al., "Xeroderma pigmentosum and acute myeloid leukemia: a case report," Journal of Medical Case Reports, vol. 15, no. 1, p. 437, 2021. [15] P. Wang, J. Ouyang, Z. Jia, A. Zhang, and Y. Yang, "Roles of DNA damage in renal tubular epithelial cells injury," Frontiers in Physiology, vol. 14, p. 1162546, 2023. [16] N. Rex, A. Melk, and R. Schmitt, "Cellular senescence and kidney aging," Clinical Science, vol. 137, no. 24, pp. 1805-1821, 2023. [17] H. Mohrenweiser et al., "Refined mapping of the three DNA repair genes, ERCC1, ERCC2, and XRCC1, on human chromosome 19," Cytogenetic and Genome Research, vol. 52, no. 1-2, pp. 11-14, 1989. [18] R. E. London, "The structural basis of XRCC1-mediated DNA repair," DNA repair, vol. 30, pp. 90-103, 2015. [19] W. M. Radwan, H. S. Elbarbary, and N. M. Alsheikh, "DNA repair genes XPD and XRCC1 polymorphisms and risk of end-stage renal disease in Egyptian population," Renal Failure, vol. 37, no. 1, pp. 122-128, 2015. [20] M. Yin, D. Tan, and Q. Wei, "Genetic variants of the XRCC1 gene and susceptibility to esophageal cancer: a meta-analysis," International Journal of Clinical and Experimental Medicine, vol. 2, no. 1, p. 26, 2009. [21] D. M. Abd EL-Hassib, M. A. Zidan, M. M. El Amawy, H. A. Hegazy, and S. G. Ameen, "Polymorphism of XRCC1 Arg399Gln may predict for development of end-stage renal disease. A PCR confirmed case-control study," Meta Gene, vol. 29, p. 100915, 2021. [22] S. Lu and E. Cosgun, "Boosting GPT models for genomics analysis: generating trusted genetic variant annotations and interpretations through RAG and Fine-tuning," Bioinformatics advances, vol. 5, no. 1, p. vbaf019, 2025. [23] A. Changalidis, Y. Barbitoff, Y. Nasykhova, and A. Glotov, "A systematic review on the generative AI applications in human medical genetics," Frontiers in Genetics, vol. 16, p. 1694070, 2026. [24] O. Abdelwahab and D. Torkamaneh, "Artificial intelligence in variant calling: a review," Frontiers in Bioinformatics, vol. 5, p. 1574359, 2025. [25] V. S. Lee et al., "Computational screening and identifying binding interaction of anti-viral and anti-malarial drugs: Toward the potential cure for SARS-CoV-2," Progress in Drug Discovery & Biomedical Science, vol. 3, no. 1, 2020. [26] F. Esteves, J. Rueff, and M. Kranendonk, "The central role of cytochrome P450 in xenobiotic metabolism—a brief review on a fascinating enzyme family," Journal of xenobiotics, vol. 11, no. 3, pp. 94-114, 2021. [27] N. A. Abdelsalam, A. T. Ramadan, M. T. ElRakaiby, and R. K. Aziz, "Toxicomicrobiomics: the human microbiome vs. pharmaceutical, dietary, and environmental xenobiotics," Frontiers in pharmacology, vol. 11, p. 390, 2020. [28] F. R. Pinu et al., "Systems biology and multi-omics integration: viewpoints from the metabolomics research community," Metabolites, vol. 9, no. 4, p. 76, 2019. [29] R. J. Hung, J. Hall, P. Brennan, and P. Boffetta, "Genetic polymorphisms in the base excision repair pathway and cancer risk: a HuGE review," American journal of epidemiology, vol. 162, no. 10, pp. 925-942, 2005. [30] M. Szatkowska and J. Zdrada-Nowak, "Genetic Polymorphisms in Base Excision Repair (BER) and Nucleotide Excision Repair (NER) Pathways as Potential Biomarkers for Gynecological Cancers: A Comprehensive Literature Review," Cancers, vol. 17, no. 13, p. 2170, 2025. | ||
|
Statistics Article View: 295 PDF Download: 291 |
||