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DNA Repair Enzyme XRCC4 30 bp Indel Intron 3 Locus Significant Association with Predisposition of Cataract in Senility

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Abstract

Impaired DNA damage repair cascade can disrupt the lens transparency due to aging-associated oxidative stress. The aim of study was to assess the association of 30 bp indel mutation (rs28360071) in XRCC4 gene with susceptibility of cataract in senility. The study followed case–control design with a total of n = 200 participants and divided equally into senile cataract patients and control groups. Conventional polymerase chain reaction (PCR) was performed for the genotyping of XRCC4 (rs28360071) mutation. In statistical measures, SPSS ® 20.0 software, MedCal©, and SNPStats© tools were used for data analysis. Distribution of homozygous D/D and mutant D allele was higher in senile cataract patients in comparison to controls. XRCC4 (rs28360071) mutation was significantly associated with predisposition senile cataract (χ2 = 13.96, adjusted OR = 2.29, 95% CI: 1.5–3.4, p < 0.001). Codominant model was suggested to be a best fit model. Mutant D/D genotype described significant association with LDL (adjusted OR = 1.67, 95% CI: 0.14–1.45, p = 0.03),and HDL (adjusted OR = 1.66, 95% CI: 0.92–2.31, p = 0.05) cholesterol with higher risk of senile cataract. XRCC4 (rs28360071) mutation may serve as a potential biomarker for the prognosis of cataract in senility. It can used to measure interruption in NHEJ repair pathway to indicate DNA damage in lens epithelial cells which could accelerate cataractogenesis with aging.

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Data Availability

Blood samples and history were taken after the consent of all study participants from their records at respective hospital.

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Acknowledgements

POB Eye Hospital is acknowledged for their collaboration in sample collection.

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Authors and Affiliations

  1. Faculty of Engineering, Science, Technology and Management, Department of Biomedical Engineering, Ziauddin University (ZUFESTM), F-103, Block B, North Nazimabad, Karachi, 74600, Pakistan

    Sanober Kafeel, Neelam Bizenjo, Shams Salman Shivji & Asifa Keran

  2. Dr. Zafar H. Zaidi Center for Proteomics (ZCP), University of Karachi, Karachi, 75270, Pakistan

    Zehra Hashim

  3. The Karachi Institute of Biotechnology and Genetic Engineering (KIBGE), University of Karachi, Main University Rd, Karachi, 75270, Pakistan

    Syeda Nuzhat Nawab

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  1. Sanober Kafeel
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Contributions

Sanober Kafeel: Conceptualization, Sample Collection, Data Curation, Statistical Analysis, and original draft writing. Neelam Bizenjo: Conceptualization, Methodology, Optimization, Experimental Work, Writing and Editing. Shams Salman Shivji: Conceptualization, Investigation, Literature Review, Experimental Work, Data Curation. Asifa Keran: Conceptualization, Optimization, Experimental work, Investigation, Writing Review. Zehra Hashim: Methodology, Formal analysis, Validation, Resources, Writing–Review and Editing. Syeda Nuzhat Nawab: Formal Analysis, Investigation, Writing–Review and Editing.

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Correspondence to Sanober Kafeel.

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Ethical approval from Institutional Ethical Committee of University of Karachi (Ref No. ICE/080/2016) was obtained.

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Kafeel, S., Bizenjo, N., Shivji, S.S. et al. DNA Repair Enzyme XRCC4 30 bp Indel Intron 3 Locus Significant Association with Predisposition of Cataract in Senility. Appl Biochem Biotechnol 196, 99–112 (2024). https://doi.org/10.1007/s12010-023-04533-7

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