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NFE2L2/Nrf2 (NUCLEAR FACTOR ERYTHROID 2-LIKE 2)

NFE2L2/Nrf2 (Nuclear Factor Erythroid 2 Like 2) is key to regulating the body's detoxification and antioxidant system (Su et al., 2013). It catalyzes the activation and deactivation of various aromatic amines, heterocyclic amines and hydrazine drugs (Tunali & Tiryakioglu, 2011).

Nrf2 is an important regulator in the induction of phase II antioxidant and detoxification enzyme genes that protect cells from damage resulting from oxidative and electrophilic attack (Kundu et al., 2010). When Nrf2 is activated, it dissociates from the cytosolic protein Keap1 (Kelch-like ECH-associated protein 1) and translocates to bind to AREs in the promoter/enhancer region of genes associated with phase II detoxification and antioxidant enzyme genes. Dietary phytochemicals indirectly increase cellular antioxidant capacity by increasing the gene expression of phase II antioxidant and detoxification enzymes through the Nrf2 pathway (Su et al., 2013). Nrf2 induction is thought to protect against various oxidative stress-related conditions such as cancer, kidney dysfunction, lung disorders, arthritis, neurological disease, and cardiovascular disease (Boyanapalli et al., 2014).

Phase 2-NFE2L2 (Nuclear Factor Erythroid 2 Like 2)
Genes	rs-code	Minor Allele	Minor Allele Description	Reference
NFE2L2	rs13001694	A	High relative risk for oxidative damage.	(Figarska et al., 2014 )
NFE2L2	rs1806649	C	High relative risk for oxidative damage.	(Figarska et al., 2014)
NFE2L2	rs6726395	A	High relative risk for oxidative damage.	(Synowiec et al., 2013)

The table above includes the NFE2L2 (Nuclear Factor Erythroid 2 Like 2) gene and its polymorphisms. These polymorphisms are genetic variants that may predispose a person to certain conditions or protect a person against certain conditions. Studies on these genes are as follows; It has been found that the G allele of the NFE2L2 gene rs6726395 polymorphism may play a role in the pathogenesis of age-related macular degeneration (AMD) (Synowiec et al., 2013). The risk of COPD (Chronic Obstructive Pulmonary Disease) mortality has been found to be reduced in carriers of the T allele of rs1806649, and the T allele of rs1806649 is thought to have protective potential compared to the C allele. Survival analysis of the Vlagtwedde-Vlaardingen cohort, a general population-based cohort of Caucasian individuals of Dutch descent, supports the hypothesis that Nrf2 may be a gene contributing to individual differences in human lifespan. The A/G substitution in the rs13001694 variant can only occur under conditions of oxidative stress (smoking habits) and has been associated with a lower risk of all-cause mortality (Figarska et al., 2014).

REFERENCES

Boyanapalli, S. S., Paredes-Gonzalez, X., Fuentes, F., Zhang, C., Guo, Y., Pung, D., ... & Kong, A. N. T. (2014). Nrf2 knockout attenuates the anti-inflammatory effects of phenethyl isothiocyanate and curcumin. Chemical research in toxicology, 27(12), 2036-2043. https://pubs.acs.org/doi/full/10.1021/tx500234h

Figarska, S. M., Vonk, J. M., & Boezen, H. M. (2014). NFE2L2 polymorphisms, mortality, and metabolism in the general population. Physiological Genomics, 46(12), 411-417. https://doi.org/10.1152/physiolgenomics.00178.2013

Houghton CA, Fassett RG, Coombes JS. Sulforaphane and Other Nutrigenomic Nrf2 Activators: Can the Clinician's Expectation Be Matched by the Reality? Oxid Med Cell Longev. 2016;2016:7857186. doi: 10.1155/2016/7857186. Epub 2016 Jan 6. PMID: 26881038; PMCID: PMC4736808.

Kundu, J.K., Surh, YJ. Nrf2-Keap1 Signaling as a Potential Target for Chemoprevention of Inflammation-Associated Carcinogenesis. Pharm Res 27, 999–1013 (2010). https://doi.org/10.1007/s11095-010-0096-8 . https://link.springer.com/article/10.1007/s11095-010-0096-8#citeas

Su, Z.-Y., Shu, L., Khor, T. O., Lee, J. H., Fuentes, F., & Kong, A.-N. T. (2013). A perspective on dietary phytochemicals and cancer chemoprevention: oxidative stress, nrf2, and epigenomics. Natural products in cancer prevention and therapy, 133-162. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3924422/

Synowiec, E., Sliwinski, T., Danisz, K., Blasiak, J., Sklodowska, A., Romaniuk, D., Watala, C., Szaflik, J., & Szaflik, J. P. (2013). Association between polymorphism of the NQO1, NOS3 and NFE2L2 genes and AMD. Front Biosci (Landmark Ed), 18(1), 80-90. https://doi.org/10.2741/4088

Tunali, N. E., & Tiryakioglu, N. O. (2011). Polymorphisms in the xenobiotic genes and susceptibility to bladder cancer. Journal of Cell and Molecular Biology, 9(1), 5. https://www.researchgate.net/publication/278785478_Polymorphisms_in_the_xenobiotic_genes_and_susceptibility_to_bladder_cancer

Z. Y. Su, L. Shu, T. O. Khor, J. H. Lee, F. Fuentes, and A. N. T. Kong, “A perspective on dietary phytochemicals and cancer chemoprevention: oxidative stress, Nrf2, and epigenomics,” Topics in Current Chemistry, vol. 329, pp. 133–162, 2013. https://link.springer.com/chapter/10.1007/128_2012_340