Skip to main content

Advertisement

Log in

Analysis of FOXO1A and FOXO3A gene allele association with human longevity

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

Abstract

Seeking human longevity association with gene polymorphisms in transcription factors in the Tatar ethnic group, we conducted an analysis for age-related genotype frequencies in polymorphic sites of FOXO1A (rs4943794, 72327C>G) and FOXO3A (rs3800231, 35-2764A>G) genes. Genotyping was conducted using the PCR-RFLP approach. According to the results of logistic regression analysis, during maturity and old age periods, a decrease in the number of FOXO1A*G/*G (OR = 0.984, P = 0.004) genotype carriers occurs and an increase in the number of FOXO1A*C/*G (OR = 1.035, P = 0.014) and FOXO1A*C/*C (OR = 1.024, P = 0.033) genotype carriers occurs in the sample of subjects before gender adjustments. In the sample of long-livers, the number of FOXO1A*C/*C (OR = 0.772, P = 0.028) genotype carriers decreased among women, while the number of FOXO3A*G/*G (OR = 1.008, P = 0.0001) genotype carriers increased among both men and women. Therefore, the FOXO1A gene polymorphic site rs4943794 is associated with an acquisition of old and senescent age in a sample before gender adjustments and with women’s longevity. FOXO3A gene polymorphic site rs3800231 is associated with longevity in both women and men.

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

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Similar content being viewed by others

Explore related subjects

Discover the latest articles and news from researchers in related subjects, suggested using machine learning.

References

  1. Deelen, J., Beekman, M., Uh, H.W., et al., Genomewide association meta-analysis of human longevity identifies a novel locus conferring survival beyond 90 years of age, Hum. Mol. Genet., 2014, vol. 23, no. 16, pp. 4420–4432.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Hjelmborg, J.B., Iachine, I., Skytthe, A., et al., Genetic influence on human lifespan and longevity, Hum. Genet., 2006, vol. 119, pp. 312–321.

    Article  Google Scholar 

  3. Gögele M., Pattaro, C., Fuchsberger, C., et al., Heritability analysis of life span in a semi-isolated population followed across four centuries reveals the presence of pleiotropy between life span and reproduction, J. Gerontol. Biol. Sci. Med. Sci., 2010, vol. 66, pp. 26–37.

  4. Tullet, J.M., Araiz, C., Sanders, M.J., et al., DAF16/FoxO directly regulates an atypical AMP-activated protein kinase gamma isoform to mediate the effects of insulin/IGF-1 signaling on aging in Caenorhabditis elegans, PLoS Genet., 2014, vol. 10, no. 2. e1004109

    Article  PubMed  PubMed Central  Google Scholar 

  5. Di Bona, D., Accardi, G., Virruso, C., et al., Association between genetic variations in the insulin/insulinlike growth factor (Igf-1) signaling pathway and longevity: a systematic review and meta-analysis, Curr. Vascular Pharmacol., 2014, vol. 12, no. 5, pp. 674–681.

    Article  Google Scholar 

  6. Webb, A.E. and Brunet, A., FOXO transcription factors: key regulators of cellular quality control, Trends Biochem. Sci., 2014, vol. 39, no. 4, pp. 159–169.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Böttcher Y., Tönjes, A., Enigk, B., et al., A SNP haplotype of the forkhead transcription factor FOXO1A gene may have a protective effect against type 2 diabetes in German Caucasians, Diabetes Metabol., 2007, vol. 33, no. 4, pp. 277–283.

    Article  Google Scholar 

  8. Willcox, B.J., Donlon, T.A., He, Q., et al., FOXO3A genotype is strongly associated with human longevity, Proc. Natl. Acad. Sci. U.S.A., 2008, vol. 105, no. 37, pp. 13987–13992.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Flachsbart, F., Caliebe, A., Kleindorp, R., et al., Association of FOXO3A variation with human longevity confirmed in German centenarians, Proc. Natl. Acad. Sci. U.S.A., 2009, vol. 106, no. 8, pp. 2700–2705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Anselmi, C.V., Malovini, A., Roncarati, R., et al., Association of the FOXO3A locus with extreme longevity in a southern Italian centenarian study, Rejuvenation Res., 2009, vol. 12, no. 2, pp. 95–104.

    Article  CAS  PubMed  Google Scholar 

  11. Pawlikowska, L., Hu, D., Huntsman, S., et al., Association of common genetic variation in the insulin/IGF1 signaling pathway with human longevity, Aging Cell, 2009, vol. 8, no. 4, pp. 460–472.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Soerensen, M., Dato, S., Christensen, K., et al., Replication of an association of variation in the FOXO3A gene with human longevity using both case-control and longitudinal data, Aging Cell, 2010, vol. 9, no. 6, pp. 1010–1017.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lunetta, K.L., D’Agostino, R.B., Karasik, D., et al., Genetic correlates of longevity and selected age-related phenotypes: a genome-wide association study in the Framingham study, BMC Med. Genet., 2007, vol. 8, suppl. 1, p. S13.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Kleindorp, R., Flachsbart, F., Puca, A.A., et al., Candidate gene study of FOXO1, FOXO4, and FOXO6 reveals no association with human longevity in Germans, Aging Cell, 2011, vol. 10, no. 4, pp. 622–628.

    CAS  PubMed  Google Scholar 

  15. Sambrook, J., Fritsch, E.F., and Maniatis, T., Molecular Cloning: A Laboratory Manual, New York: Cold Spring Harbor Lab., 1989, 2nd ed.

    Google Scholar 

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

    Google Scholar 

  17. Relling, D.P., Esberg, L.B., Fang, C.X., et al., High-fat diet-induced juvenile obesity leads to cardiomyocyte dysfunction and upregulation of Foxo3a transcription factor independent of lipotoxicity and apoptosis, J. Hypertens., 2006, vol. 24, no. 3, pp. 549–561.

    Article  CAS  PubMed  Google Scholar 

  18. Li, H.H., Willis, M.S., Lockyer, P., et al., Atrogin-1 inhibits Akt-dependent cardiac hypertrophy in mice via ubiquitin-dependent coactivation of forkhead proteins, J. Clin. Invest., 2007, vol. 117, no. 11, pp. 3211–3223.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ni, Y.G., Berenji, K., Wang, N., et al., Foxo transcription factors blunt cardiac hypertrophy by inhibiting calcineurin signaling, Circulation, 2006, vol. 114, no. 11, pp. 1159–1168.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Dbek, J., Owczarek, A., Gsior, Z., et al., Oligonucleotide microarray analysis of genes regulating apoptosis in chronically ischemic and postinfarction myocardium, Biochem. Genet., 2008, vol. 46, nos. 5–6, pp. 241–247.

    Article  Google Scholar 

  21. Barger, J.L., Kayo, T., Pugh, T.D., et al., Short-term consumption of a resveratrol-containing nutraceutical mixture mimics gene expression of long-term caloric restriction in mouse heart, Exp. Gerontol., 2008, vol. 43, no. 9, pp. 859–866.

    Article  CAS  PubMed  Google Scholar 

  22. Traylor, M., Farrall, M., Holliday, E.G., et al., Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE collaboration): a meta-analysis of genome-wide association studies, Lancet Neurol., 2012, vol. 11, no. 11, pp. 951–962.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Li, Y., Wang, W.J., Cao, H., et al., Genetic association of FOXO1A and FOXO3A with longevity trait in Han Chinese populations, Hum. Mol. Genet., 2009, vol. 18, no. 24, pp. 4897–4904.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lutskii, M.A., Zemskov, A.M., Smelyanets, M.A., and Lushnikova, Yu.P., Formation of oxidative stress, a component of the complex pathogenesis of socially significant diseases of the nervous system—stroke and multiple sclerosis, Fundam. Nauki, 2014, no. 10, pp. 924–929.

    Google Scholar 

  25. Kuningas, M., Haplotypes in the human Foxo1a and Foxo3a genes; impact on disease and mortality at old age, Eur. J. Num. Genet., 2007, vol. 15, no. 3, pp. 294–301.

    Article  CAS  Google Scholar 

  26. Mußsig, K., Staiger, H., Machicao, F., et al., Association of common genetic variation in the FOXO1 gene with β-cell dysfunction, impaired glucose tolerance, and type 2 diabetes, J. Clin. Endocrinol. Metabol., 2009, vol. 94, no. 4, pp. 1353–1360.

    Google Scholar 

  27. Accili, D. and Arden, K.C., FoxOs at the crossroads of cellular metabolism, differentiation, and transformation, Cell, 2004, vol. 117, no. 4, pp. 421–426.

    CAS  PubMed  Google Scholar 

  28. Estall, J.D., The Foxo family: partners in crime or silent heroes, Endocrinology, 2012, vol. 153, no. 2, pp. 549–551.

    Article  CAS  PubMed  Google Scholar 

  29. Nabarro, S., Himoudi, N., Papanastasiou, A., et al., Coordinated oncogenic transformation and inhibition of host immune responses by the PAX3-FKHR fusion oncoprotein, J. Exp. Med., 2005, vol. 202, no. 10, pp. 1399–1410.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Katoh, M. and Katoh, M., Human FOX gene family (review), Int. J. Oncol., 2004, vol. 25, no. 5, pp. 1495–1500.

    CAS  PubMed  Google Scholar 

  31. Boreddy, S.R., Pramanik, K.C., and Srivastava, S.K., Pancreatic tumor suppression by benzyl isothiocyanate is associated with inhibition of PI3K/AKT/FOXO pathway, Clin. Cancer. Res., 2011, vol. 17, no. 7, pp. 1784–1795.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Moran, A., Jacobs, D.R., Steinberger, J., et al., Changes in insulin resistance and cardiovascular risk during adolescence establishment of differential risk in males and females, Circulation, 2008, vol. 117, no. 18, pp. 2361–2368.

    Article  CAS  PubMed  Google Scholar 

  33. Gómez-Pérez, Y., Amengual-Cladera, E., CatalàNiell, A., et al., Gender dimorphism in high-fat-dietinduced insulin resistance in skeletal muscle of aged rats, Cell. Physiol. Biochem., 2008, vol. 22, nos. 5–6, pp. 539–548.

    PubMed  Google Scholar 

  34. Galipeau, D., Verma, S., and McNeill, J.H., Female rats are protected against fructose-induced changes in metabolism and blood pressure, Am. J. Physiol.—Heart Circ. Physiol., 2002, vol. 283, no. 6, pp. H2478–H2484.

    Article  CAS  PubMed  Google Scholar 

  35. Hevener, A., Reichart, D., Janez, A., et al., Female rats do not exhibit free fatty acid-induced insulin resistance, Diabetes, 2002, vol. 51, no. 6, pp. 1907–1912.

    Article  CAS  PubMed  Google Scholar 

  36. Desrois, M., Lan, C., Dalmasso, C., et al., TOPIC 02Diabetes, dyslipidemia, metabolism, Arch. Cardiovasc. Dis., 2011, vol. 2, suppl., pp. 1–91.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to V. V. Erdman.

Additional information

Original Russian Text © V.V. Erdman, T.R. Nasibullin, I.A. Tuktarova, R.Sh. Somova, O.E. Mustafina, 2016, published in Genetika, 2016, Vol. 52, No. 4, pp. 474–481.

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. Analysis of FOXO1A and FOXO3A gene allele association with human longevity. Russ J Genet 52, 416–422 (2016). https://doi.org/10.1134/S1022795416020034

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S1022795416020034

Keywords