The role of rs713041 glutathione peroxidase 4 (GPX4) single nucleotide polymorphism on disease susceptibility in humans: a systematic review and meta-analysis.

Barbosa, Priscila; Abo El-Magd, Nada F.; Hesketh, John; Bermano, Giovanna

Abstract

The single-nucleotide polymorphism (SNP) rs713041, located in the regulatory region, is required to incorporate selenium into the selenoprotein glutathione peroxidase 4 (GPX4) and has been found to have functional consequences. This systematic review aimed to conduct a meta-analysis to determine whether there is an association between GPX4 (rs713041) SNP and the risk of diseases in humans and its correlation with selenium status. Material and methods: A systematic search for English-language manuscripts published between January 1990 and November 2022 was carried out using six databases: CINAHL, Cochrane, Medline, PubMed, Scopus and Web of Science. Odds ratios (ORs) and 95% confidence intervals (CIs) were applied to assess a relationship between GPX4 (rs713041) SNP and the risk of different diseases based on three genetic models. Review Manager 5.4 and Comprehensive Meta-Analysis 4 software were used to perform the meta-analysis and carry out Egger's test for publication bias. Results: Data from 21 articles were included in the systematic review. Diseases were clustered according to the physiological system affected to understand better the role of GPX4 (rs713041) SNP in developing different diseases. Carriers of the GPX4 (rs173041) T allele were associated with an increased risk of developing colorectal cancer in additive and dominant models (p = 0.02 and p = 0.004, respectively). In addition, carriers of the T allele were associated with an increased risk of developing stroke and hypertension in the additive, dominant and recessive models (p = 0.002, p = 0.004 and p = 0.01, respectively). On the other hand, the GPX4 (rs713041) T allele was associated with a decreased risk of developing pre-eclampsia in the additive, dominant and recessive models (p < 0.0001, p = 0.002 and p = 0.0005, respectively). Moreover, selenium levels presented lower mean values in cancer patients relative to control groups (SMD = −0.39 µg/L; 95% CI: −0.64, −0.14; p = 0.002, I2 = 85%). Conclusion: GPX4 (rs713041) T allele may influence colorectal cancer risk, stroke, hypertension and pre-eclampsia. In addition, low selenium levels may play a role in the increased risk of cancer.

Citation

BARBOSA, P., ABO EL-MAGD, N.F., HESKETH, J. and BERMANO, G. 2022. The role of rs713041 glutathione peroxidase 4 (GPX4) single nucleotide polymorphism on disease susceptibility in humans: a systematic review and meta-analysis. International journal of molecular sciences [online], 23(24), article 15762. Available from: https://doi.org/10.3390/ijms232415762

• Journal Article Type: Review
• Acceptance Date: Dec 8, 2022
• Online Publication Date: Dec 12, 2022
• Publication Date: Dec 31, 2022
• Deposit Date: Dec 13, 2022
• Publicly Available Date: Dec 13, 2022
• Journal: International journal of molecular sciences
• Print ISSN: 1661-6596
• Electronic ISSN: 1422-0067
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 23
• Issue: 24
• Article Number: 15762
• DOI: https://doi.org/10.3390/ijms232415762
• Keywords: Genetic polymorphism; Glutathione peroxidase 4; Human disease; Meta-analysis
• Public URL: https://rgu-repository.worktribe.com/output/1839743
• Additional Information: This article has been published with separate supporting information. This supporting information has been incorporated into a single file on this repository and can be found at the end of the accompanying document.