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.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
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.
Hjelmborg, J.B., Iachine, I., Skytthe, A., et al., Genetic influence on human lifespan and longevity, Hum. Genet., 2006, vol. 119, pp. 312–321.
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.
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
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Sambrook, J., Fritsch, E.F., and Maniatis, T., Molecular Cloning: A Laboratory Manual, New York: Cold Spring Harbor Lab., 1989, 2nd ed.
Khrisanfova, E.N., Osnovy gerontologii (antropologicheskie aspekty) (Fundamentals of Gerontology (Anthropological Aspects)), Moscow: VLADOS, 1999.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Estall, J.D., The Foxo family: partners in crime or silent heroes, Endocrinology, 2012, vol. 153, no. 2, pp. 549–551.
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.
Katoh, M. and Katoh, M., Human FOX gene family (review), Int. J. Oncol., 2004, vol. 25, no. 5, pp. 1495–1500.
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.
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.
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.
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.
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.
Desrois, M., Lan, C., Dalmasso, C., et al., TOPIC 02Diabetes, dyslipidemia, metabolism, Arch. Cardiovasc. Dis., 2011, vol. 2, suppl., pp. 1–91.
Author information
Authors and Affiliations
Corresponding author
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
About this article
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1134/S1022795416020034