Skip to main content
SpringerLink
Log in

The Study of Association of Polymorphic Markers of the SOD1, SOD2, and SOD3 Genes with Longevity

  • HUMAN GENETICS
  • Published:
Russian Journal of Genetics Aims and scope Submit manuscript

Abstract

For the first time, a study of genetic factors of longevity was conducted in the prevalent populations of 2511 residents of the Republic of Bashkortostan—Russians, Bashkirs, and Tatars. We investigated the polymorphic markers in the genes of the antioxidant defense enzymes—SOD1 (rs2070424), SOD2 (rs4880), and SOD3 (rs1799895). We detected ethnicity-specific patterns of the distribution of genotype frequencies between Bashkir and Russian groups (rs2070424 of the SOD1 gene, P = 0.003), as well as between Tatars and the groups of Russians and Bashkirs (rs4880 of the SOD2 gene, P < 0.001 and 0.035, respectively). We found associations of the polymorphic markers in SOD family genes with age. Among Russians, the chances to attain longevity were higher in the SOD1*А/А genotype carriers (OR = 1.025, P = 0.001) and lower in those with the SOD1*А/G (OR = 0.975, Р = 0.001) and SOD2*А/А (OR = 0.985, Р = 0.002) genotypes. Among Tatars, we observed a decrease in the SOD2*A/A (OR = 0.989, Р = 0.029) and SOD2*V/V (OR = 0.985, Р < 0.001) genotype frequencies and an increase in the SOD2*A/V genotype frequency (OR = 1.023, P < 0.001). The analysis of genotype and/or allelic combinations of the studied polymorphic loci revealed 12 patterns associated with longevity among Tatars. The SOD1*А and SOD3*С alleles were present in most of the identified combinations. The SOD2 rs4880 polymorphic marker was indicative of longevity: combinations including the SOD2*V/V genotype were associated with lower chances of achieving longevity (OR ≤ 0.45, PFDR ≤ 0.0003), and combinations including the SOD2*A/V genotype were associated with higher chances of achieving longevity (OR ≥ 2.92, PFDR ≤ 1.24 × 10–6).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Il’nitskii, A.N., Proshchaev, K.I., Mateiovska-Kubeshova, Kh., et al., Age-related vitality in gerontology and geriatrics (a review), Nauchn. Rezul’t. Biomed. Issled., 2019, vol. 5, no. 4, pp. 102—116. https://doi.org/10.18413/2658-6533-2019-5-4-0-8

    Article  Google Scholar 

  2. Volykhina, V.E. and Shafranovskaya, E.V., Superoxide dismutases: structure and properties, Vestn. Vitebsk. Gos. Med. Univ., 2009, vol. 8, no. 4, pp. 1—18.

  3. Novikov, V.E., Levchenkova, O.S., and Pozhilova, E.V., The role of reactive oxygen forms in the cell physiology and pathology and their pharmacological regulation, Obz. Klin. Farmakol. Lek. Ter., 2014, vol. 12, no. 4, pp. 13—21.

    Article  Google Scholar 

  4. Orr, W.C. and Sohal, R.S., Extension of life-span by overexpression of superoxide dismutase and catalase in Drosophila melanogaster, Science, 1994, vol. 263, no. 5150, pp. 1128—1130. https://doi.org/10.1126/science.8108730

    Article  CAS  PubMed  Google Scholar 

  5. Parkes, T.L., Elia, A.J., Dickinson, D., et al., Extension of Drosophila lifespan by overexpression of human SOD1 in motorneurons, Nat. Genet., 1998, vol. 19, no. 2, pp. 171—174.

    Article  CAS  Google Scholar 

  6. Lewandowski, Ł., Kepinska, M., and Milnerowicz, H., The copper-zinc superoxide dismutase activity in selected diseases, Eur. J. Clin. Invest., 2019, vol. 49, no. 1. e13036. https://doi.org/10.1111/eci.13036

    Article  CAS  PubMed  Google Scholar 

  7. Mathew, C.C., The isolation of high molecular weight eukaryotic DNA, Methods in Molecular Biology, Walker, J.M., Ed., New York: Haman Press, 1984, pp. 31—34.

    Google Scholar 

  8. Khrisanfova, E.N., Osnovy gerontologii (antropologicheskie aspekty) (Fundamentals of Gerontology (Anthropological Aspects)), Moscow: Vlados, 1999.

  9. Favorov, A.V., Andreewski, T.V., Sudomoina, M.A., et al., A Markov chain Monte Carlo technique for identification of combinations of allelic variants underlying complex diseases in humans, Genetics, 2005, vol. 171, no. 4, pp. 2113—2121. https://doi.org/10.1534/genetics.105.048090

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Fabrizio, P., Liou, L.L., Moy, V.N., et al., SOD2 functions downstream of Sch9 to extend longevity in yeast, Genetics, 2003, vol. 163, no. 1, pp. 35—46.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Hu, D., Cao, P., Thiels, E., et al., Hippocampal long-term potentiation, memory, and longevity in mice that overexpress mitochondrial superoxide dismutase, Neurobiol. Learn. Mem., 2007, vol. 87, no. 3, pp. 372—384. https://doi.org/10.1016/j.nlm.2006.10.003

    Article  CAS  PubMed  Google Scholar 

  12. Potukuchi, A., Addepally, U., Sindhu, K., and Manchala, R., Increased total DNA damage and oxidative stress in brain are associated with decreased longevity in high sucrose diet fed WNIN/Gr-Ob obese rats, Nutr. Neurosci., 2018, vol. 21, no. 9, pp. 648—656. https://doi.org/10.1080/1028415X.2017.1332509

    Article  CAS  PubMed  Google Scholar 

  13. Lin C., Zhang X., Xiao J. et al. Effects on longevity extension and mechanism of action of carnosic acid in Caenorhabditis elegans, Food Funct., 2019, vol. 10, no. 3, pp. 1398—1410. https://doi.org/10.1039/C8FO02371A

    Article  PubMed  Google Scholar 

  14. Otaki, Y., Watanabe, T., Nishiyama, S., et al., The impact of superoxide dismutase-1 genetic variation on cardiovascular and all-cause mortality in a prospective cohort study: the Yamagata (Takahata) study, PLoS One, 2016, vol. 11, no. 10. e0164732. https://doi.org/10.1371/journal.pone.0164732

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Spisak, K., Klimkowicz-Mrowiec, A., Pera, J., et al., rs2070424 of the SOD1 gene is associated with risk of Alzheimer’s disease, Neurol. Neurochir. Pol., 2014, vol. 48, no. 5, pp. 342—345. https://doi.org/10.1016/j.pjnns.2014.09.002

    Article  PubMed  Google Scholar 

  16. El-Kheshen, G., Moeini, M., and Saadat, M., Susceptibility to ulcerative colitis and genetic polymorphisms of A251G SOD1 and C-262T CAT, J. Med. Biochem., 2016, vol. 35, no. 3, pp. 333—336. https://doi.org/10.1515/jomb-2016-0002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Haldar, S.R., Chakrabarty, A., Chowdhury, S., et al., Oxidative stress-related genes in type 2 diabetes: association analysis and their clinical impact, Biochem. Genet., 2015, vol. 53, nos. 4—6, pp. 93—119. https://doi.org/10.1007/s10528-015-9675-z

    Article  CAS  PubMed  Google Scholar 

  18. Hernández-Guerrero, C., Hernández-Chávez, P., Romo-Palafox, I., et al., Genetic polymorphisms in SOD (rs2070424, rs7880) and CAT (rs7943316, rs1001179) enzymes are associated with increased body fat percentage and visceral fat in an obese population from Central Mexico, Arch. Med. Res., 2016, vol. 47, no. 5, pp. 331—339. https://doi.org/10.1016/j.arcmed.2016.08.007

    Article  CAS  PubMed  Google Scholar 

  19. Kase, B.A., Northrup, H., Morrison, A.C., et al., Association of copper—zinc superoxide dismutase (SOD1) and manganese superoxide dismutase (SOD2) genes with nonsyndromic myelomeningocele, Birth Defects Res., Part A, 2012, vol. 94, no. 10, pp. 762—769. https://doi.org/10.1002/bdra.23065

    Article  CAS  Google Scholar 

  20. Dato, S., Sørensen, M., Lagani, V., et al., Contribution of genetic polymorphisms on functional status at very old age: a gene-based analysis of 38 genes (311 SNPs) in the oxidative stress pathway, Exp. Gerontol., 2014, vol. 52, pp. 23—29. https://doi.org/10.1016/j.exger.2014.01.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gentschew, L., Flachsbart, F., Kleindorp, R., et al., Polymorphisms in the superoxidase dismutase genes reveal no association with human longevity in Germans: a case-control association study, Biogerontology, 2013, vol. 14, no. 6, p. 719—727. https://doi.org/10.1007/s10522-013-9470-3

    Article  CAS  PubMed  Google Scholar 

  22. Ebrahimpour, S. and Saadat, I., Association of CAT C-262T and SOD1 A251G single nucleotide polymorphisms susceptible to gastric cancer, Mol. Biol. Res. Commun., 2014, vol. 3, no. 4, pp. 223—229.

    PubMed  PubMed Central  Google Scholar 

  23. Kolesnikova, L., Bairova, T.A., and Pervushina, O.A., Genes of the antioxidant system enzymes, Vestn. Ross. Akad. Med. Nauk, 2013, vol. 68, no. 12, pp. 83—88.

    Article  Google Scholar 

  24. Sutton, A., Imbert, A., Igoudjil, A., et al., The manganese superoxide dismutase Ala16Val dimorphism modulates both mitochondrial import and mRNA stability, Pharmacogenet. Genomics, 2005, vol. 15, no. 5, pp. 311—319.

    Article  CAS  Google Scholar 

  25. Blein, S., Berndt, S., Joshi, A.D., et al., Factors associated with oxidative stress and cancer risk in the Breast and Prostate Cancer Cohort Consortium, Free Radical Res., 2014, vol. 48, no. 3, pp. 380—386. https://doi.org/10.3109/10715762.2013.875168

    Article  CAS  Google Scholar 

  26. Jones, D.A., Prior, S.L., Tang, T.S., et al., Association between the rs4880 superoxide dismutase 2 (C>T) gene variant and coronary heart disease in diabetes mellitus, Diabetes Res. Clin. Pract., 2010, vol. 90, no. 2, pp. 196—201. https://doi.org/10.1016/j.diabres.2010.07.009

    Article  CAS  PubMed  Google Scholar 

  27. Liu, C., Fang, J., and Liu, W., Superoxide dismutase coding of gene polymorphisms associated with susceptibility to Parkinson’s disease, J. Integr. Neurosci., 2019, vol. 18, no. 3, pp. 299—303. https://doi.org/10.31083/j.jin.2019.03.127

    Article  PubMed  Google Scholar 

  28. Tian, C., Fang, S., Du, X., and Jia, C., Association of the C47T polymorphism in SOD2 with diabetes mellitus and diabetic microvascular complications: a meta-analysis, Diabetologia, 2011, vol. 54, no. 4, pp. 803—811. https://doi.org/10.1007/s00125-010-2004-5

    Article  CAS  PubMed  Google Scholar 

  29. Wiener, H.W., Perry, R.T., Chen, Z., et al., A polymorphism in SOD2 is associated with development of Alzheimer’s disease, Genes Brain Behav., 2007, vol. 6, no. 8, pp. 770—776. https://doi.org/10.1111/j.1601-183X.2007.00308.x

    Article  CAS  PubMed  Google Scholar 

  30. Shimoda-Matsubayashi, S., Matsumine, H., Kobayashi, T., et al., Structural dimorphism in the mitochondrial targeting sequence in the human manganese superoxide dismutase gene: a predictive evidence for conformational change to influence mitochondrial transport and a study of allelic association in Parkinson’s disease, Biochem. Biophys. Res. Commun., 1996, vol. 226, no. 2, pp. 561—565. https://doi.org/10.1006/bbrc.1996.1394

    Article  CAS  PubMed  Google Scholar 

  31. Salminen, L.E., Schofield, P.R., Pierce, K.D., et al., Vulnerability of white matter tracts and cognition to the SOD2 polymorphism: a preliminary study of antioxidant defense genes in brain aging, Behav. Brain Res., 2017, vol. 329, pp. 111—119. https://doi.org/10.1016/j.bbr.2017.04.041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Andersen, H.R., Jeune, B., Nybo, H., et al., Low activity of superoxide dismutase and high activity of glutathione reductase in erythrocytes from centenarians, Age Ageing, 1998, vol. 27, no. 5, pp. 643—648. https://doi.org/10.1093/ageing/27.5.643

    Article  CAS  PubMed  Google Scholar 

  33. De Benedictis, G., Carotenuto, L., Carrieri, G., et al., Gene/longevity association studies at four autosomal loci (REN, THO, PARP, SOD2), Eur. J. Hum. Genet., 1998, vol. 6, no. 6, pp. 534—541.

    Article  CAS  Google Scholar 

  34. Kaszubowska, L., Foerster, J., Kaczor, J.J., et al., Expression of cellular protective proteins SIRT1, HSP70 and SOD2 correlates with age and is significantly higher in NK cells of the oldest seniors, Immun. Ageing, 2017, vol. 14, no. 1, pp. 3—16. https://doi.org/10.1186/s12979-017-0085-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Soerensen, M., Christensen, K., Stevnsner, T., and Christiansen, L., The Mn-superoxide dismutase single nucleotide polymorphism rs4880 and the glutathione peroxidase 1 single nucleotide polymorphism rs1050450 are associated with aging and longevity in the oldest old, Mech. Ageing Dev., 2009, vol. 130, no. 5, pp. 308—314. https://doi.org/10.1016/j.mad.2009.01.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Sandström, J., Nilsson, P., Karlsson, K., and Marklund, S.L., 10-Fold increase in human plasma extracellular superoxide dismutase content caused by a mutation in heparin-binding domain, J. Biol. Chem., 1994, vol. 269, no. 29, pp. 19163—19166.

    PubMed  Google Scholar 

  37. Kobylecki, C.J., Afzal, S., and Nordestgaard, B.G., Genetically low antioxidant protection and risk of cardiovascular disease and heart failure in diabetic subjects, EBioMedicine, 2015, vol. 2, no. 12, pp. 2010—2015. https://doi.org/10.1016/j.ebiom.2015.11.026

    Article  PubMed  PubMed Central  Google Scholar 

  38. Kobylecki, C.J., Afzal, S., and Nordestgaard, B.G., Does SOD3 R213G homozygosity influence morbidity, mortality, and lung function in the general population?, Antioxid. Redox Signaling, 2016, vol. 24, no. 15, pp. 884—891 https://doi.org/10.1089/ars.2016.6629

    Article  CAS  Google Scholar 

Download references

Funding

The study present was partially supported by the Russian Foundation for Basic Research and ASA (project no. 19-54-40007) and State Contract of the Ministry of Science and Education of the Russian Federation (no. АААА-А16-116020350032-1). DNA samples for the study were taken from the collection of human biological materials of the Institute of Biochemistry and Genetics developed within the project no. 007-030164/2. The study was conducted using the equipment provided by the Center for Shared Access Biomics and USE KODINK (Institute of Biochemistry and Genetics).

Author information

Authors and Affiliations

  1. Institute of Biochemistry and Genetics, Ufa Federal Research Centre, Russian Academy of Sciences, 450054, Ufa, Russia

    V. V. Erdman, T. R. Nasibullin, I. A. Tuktarova, Y. R. Timasheva & O. E. Mustafina

  2. Bashkir State Medical University, 450008, Ufa, Russia

    K. V. Danilko & T. V. Viktorova

Authors
  1. V. V. Erdman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. R. Nasibullin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I. A. Tuktarova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Y. R. Timasheva
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K. V. Danilko
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. T. V. Viktorova
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. O. E. Mustafina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to V. V. Erdman.

Ethics declarations

Conflict of interest. The authors declare no conflict of interest.

Statement of compliance with standards of research involving humans as subjects. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent was obtained from all individual participants involved in the study.

Additional information

Translated by A. Kazantseva

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Erdman, V.V., Nasibullin, T.R., Tuktarova, I.A. et al. The Study of Association of Polymorphic Markers of the SOD1, SOD2, and SOD3 Genes with Longevity. Russ J Genet 56, 1504–1511 (2020). https://doi.org/10.1134/S1022795420120066

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1022795420120066

Keywords:

Search

Navigation