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Associations between STR autosomal markers and longevity

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Abstract

Life span is a complex and multifactorial trait, which is shaped by genetic, epigenetic, environmental, and stochastic factors. The possibility that highly hypervariable short tandem repeats (STRs) associated with longevity has been largely explored by comparing the genotypic pools of long lived and younger individuals, but results so far have been contradictory. In view of these contradictory findings, the present study aims to investigate whether HUMTHO1 and HUMCSF1PO STRs, previously associated with longevity, exert a role as a modulator of life expectancy, as well as to assess the extent to which other autosomal STR markers are associated with human longevity in population from northern Spain. To that end, 21 autosomal microsatellite markers have been studied in 304 nonagenarian individuals (more than 90 years old) and 516 younger controls of European descent. Our results do not confirm the association found in previous studies between longevity and THO1 and CSF1PO loci. However, significant association between longevity and autosomal STR markers D12S391, D22S1045, and DS441 was observed. Even more, when we compared allelic frequency distribution of the 21 STR markers between cases and controls, we found that 6 out of the 21 STRs studied showed different allelic frequencies, thus suggesting that the genomic portrait of the human longevity is far complex and probably shaped by a high number of genomic loci.

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References

  • Aznar JM et al (2014) I-DNASE21 system: development and SWGDAM validation of a new STR 21-plex reaction. Forensic Sci Int Genet 8:10–19. doi:10.1016/j.fsigen.2013.06.014

    Article  CAS  PubMed  Google Scholar 

  • Bathum L, Andersen-Ranberg K, Boldsen J, Brosen K, Jeune B (1998) Genotypes for the cytochrome P450 enzymes CYP2D6 and CYP2C19 in human longevity. Role of CYP2D6 and CYP2C19 in longevity. Eur J Clin Pharmacol 54:427–430

    Article  CAS  PubMed  Google Scholar 

  • Bladbjerg EM, Andersen-Ranberg K, de Maat MP, Kristensen SR, Jeune B, Gram J et al (1999) Longevity is independent of common variations in genes associated with cardiovascular risk. Thromb Haemost 82:1100–1105, doi:99091100

    CAS  PubMed  Google Scholar 

  • Bonifer C, Hume DA (2008) The transcriptional regulation of the colony-stimulating factor 1 receptor (CSF1R) gene during hematopoiesis. Front Biosci 13:549–560, doi:2700

    Article  CAS  PubMed  Google Scholar 

  • Broer L et al (2015) GWAS of longevity in CHARGE consortium confirms APOE and FOXO3 candidacy. The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences 70:110–118. doi:10.1093/gerona/glu166

    Article  Google Scholar 

  • Brooks-Wilson AR (2013) Genetics of healthy aging and longevity. Hum Genet 132:1323–1338. doi:10.1007/s00439-013-1342-z

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • De Benedictis G et al (1997) DNA multiallelic systems reveal gene/longevity associations not detected by diallelic systems. The APOB locus Hum Genet 99:312–318

    Article  PubMed  Google Scholar 

  • De Benedictis G et al (1998) Gene/longevity association studies at four autosomal loci (REN, THO, PARP, SOD2). Eur J Hum Genet 6:534–541. doi:10.1038/sj.ejhg.5200222

    Article  PubMed  Google Scholar 

  • Deelen J et al (2014) Genome-wide association meta-analysis of human longevity identifies a novel locus conferring survival beyond 90 years of age. Hum Mol Genet 23:4420–4432. doi:10.1093/hmg/ddu139

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Dozmorov MG et al (2009) Unique patterns of molecular profiling between human prostate cancer LNCaP and PC-3 cells. Prostate 69:1077–1090. doi:10.1002/pros.20960

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Erdemir T, Bilican B, Oncel D, Goding CR, Yavuzer U (2002) DNA damage-dependent interaction of the nuclear matrix protein C1D with translin-associated factor X (TRAX). J Cell Sci 115:207–216

    CAS  PubMed  Google Scholar 

  • Excoffier L, Lischer HE (2010) Arlequin suite ver 3.5: a new series of programs to perform population genetics analyses under Linux and Windows. Mol Ecol Resour 10:564–567. doi:10.1111/j.1755-0998.2010.02847.x

    Article  PubMed  Google Scholar 

  • Gemayel R, Vinces MD, Legendre M, Verstrepen KJ (2010) Variable tandem repeats accelerate evolution of coding and regulatory sequences. Annu Rev Genet 44:445–477. doi:10.1146/annurev-genet-072610-155046

    Article  CAS  PubMed  Google Scholar 

  • Guo J, Chen S, Huang C, Chen L, Studholme DJ, Zhao S et al (2004) MANSC: a seven-cysteine-containing domain present in animal membrane and extracellular proteins. Trends Biochem Sci 29:172–174. doi:10.1016/j.tibs.2004.02.007

    Article  CAS  PubMed  Google Scholar 

  • Haferlach C et al (2011) CDKN1B, encoding the cyclin-dependent kinase inhibitor 1B (p27), is located in the minimally deleted region of 12p abnormalities in myeloid malignancies and its low expression is a favorable prognostic marker in acute myeloid leukemia. Haematologica 96:829–836. doi:10.3324/haematol.2010.035584

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • He YH, Lu X, Bi MX, Yang LQ, Xu LY, Kong QP (2014) The reduction of vascular disease risk mutations contributes to longevity in the Chinese population. Meta Gene 2:761–768. doi:10.1016/j.mgene.2014.09.010

    Article  PubMed Central  PubMed  Google Scholar 

  • Hering S, Muller E (2001) New alleles and mutational events in D12S391 and D8S1132: sequence data from an eastern German population. Forensic Sci Int 124:187–191

    Article  CAS  PubMed  Google Scholar 

  • Herskind AM, McGue M, Holm NV, Sorensen TI, Harvald B, Vaupel JW (1996) The heritability of human longevity: a population-based study of 2872 Danish twin pairs born 1870–1900. Hum Genet 97:319–323

    Article  CAS  PubMed  Google Scholar 

  • Huckenbeck W, Scheil HG, Schmidt HD, Efremovska L, Mikerezi I (2004) Allele frequencies of D21S11, FGA, TH01, and VWA in populations of the Balkans. Hum Biol 76:943–946

    Article  CAS  PubMed  Google Scholar 

  • Hui L, Weijian Y, Xuelian D, Qigui L (2011) Variations in short tandem repeats deduced on the basis of the number of repeats and the relationship of these variations with longevity. Age (Dordr) 33:63–68. doi:10.1007/s11357-010-9160-x

    Article  Google Scholar 

  • Kalinowski ST, Taper ML, Marshall TC (2007) Revising how the computer program CERVUS accommodates genotyping error increases success in paternity assignment. Mol Ecol 16(5):1099–1106

    Article  PubMed  Google Scholar 

  • Kim S, Welsh DA, Myers L, Cherry KE, Wyckoff J, Jazwinski SM (2015) Non-coding genomic regions possessing enhancer and silencer potential are associated with healthy aging and exceptional survival. Oncotarget 6:3600–3612, doi:2877

    Article  PubMed Central  PubMed  Google Scholar 

  • Malek TR, Castro I (2010) Interleukin-2 receptor signaling: at the interface between tolerance and immunity. Immunity S1074-7613(10):00287–6. doi:10.1016/j.immuni.2010.08.004

    Google Scholar 

  • McGue M, Vaupel JW, Holm N, Harvald B (1993) Longevity is moderately heritable in a sample of Danish twins born 1870–1880. J Gerontol 48:B237–B244

    Article  CAS  PubMed  Google Scholar 

  • Menashe I, Rosenberg PS, Chen BE (2008) PGA: power calculator for case–control genetic association analyses. BMC Genet 9:36. doi:10.1186/1471-2156-9-36

    Article  PubMed Central  PubMed  Google Scholar 

  • Minster RL et al. (2015) Genome-wide association study and linkage analysis of the healthy aging index. J Gerontol A Biol Sci Med Sci doi:10.1093/gerona/glv006

  • Park S (2001) The Excel microsatellite toolkit. Trypanotolerance in west African cattle and the population genetic effects of selection. Ph.D thesis, University of Dublin, Dublin, Ireland

  • Riley DE, Krieger JN (2005) Short tandem repeat (STR) replacements in UTRs and introns suggest an important role for certain STRs in gene expression and disease. Gene 344:203–211. doi:10.1016/j.gene.2004.09.034

    Article  CAS  PubMed  Google Scholar 

  • Schachter F, Faure-Delanef L, Guenot F, Rouger H, Froguel P, Lesueur-Ginot L et al (1994) Genetic associations with human longevity at the APOE and ACE loci. Nat Genet 6:29–32. doi:10.1038/ng0194-29

    Article  CAS  PubMed  Google Scholar 

  • Slagboom PE et al (2011) Genomics of human longevity. Philos Trans R Soc Lond B Biol Sci 366:35–42. doi:10.1098/rstb.2010.0284

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tan Q et al (2001a) Measuring the genetic influence in modulating the human life span: gene-environment interaction and the sex-specific genetic effect. Biogerontology 2:141–153

    Article  CAS  PubMed  Google Scholar 

  • Tan Q et al (2001b) Variations of cardiovascular disease associated genes exhibit sex-dependent influence on human longevity. Exp Gerontol 36:1303–1315, doi:S0531-5565(01)00102-4

    Article  CAS  PubMed  Google Scholar 

  • Tan Q et al (2002) The influences on human longevity by HUMTHO1.STR polymorphism (tyrosine hydroxylase gene). A relative risk approach. Mech Ageing Dev 123:1403–1410, doi:S0047637402000817

    Article  CAS  PubMed  Google Scholar 

  • Toth G, Gaspari Z, Jurka J (2000) Microsatellites in different eukaryotic genomes: survey and analysis. Genome Res 10:967–981

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • vB Hjelmborg J et al (2006) Genetic influence on human lifespan and longevity. Hum Genet 119:312–321. doi:10.1007/s00439-006-0144-y

  • von Wurmb-Schwark N, Caliebe A, Schwark T, Kleindorp R, Poetsch M, Schreiber S et al (2011) Association of TH01 with human longevity revisited. Eur J Hum Genet 19:924–927. doi:10.1038/ejhg.2011.43, ejhg201143

    Article  Google Scholar 

  • Wu W et al (2006) Advertisement mutational analysis of candidate genes at 12P12-13 in prostate carcinoma. Proc Amer Assoc Cancer Res 47

  • Yashin AI et al (1999) Genes, demography, and life span: the contribution of demographic data in genetic studies on aging and longevity. Am J Hum Genet 65:1178–1193. doi:10.1086/302572

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Zheng L, Sharma R, Gaskin F, Fu SM, Ju ST (2007) A novel role of IL-2 in organ-specific autoimmune inflammation beyond regulatory T cell checkpoint: both IL-2 knockout and Fas mutation prolong lifespan of Scurfy mice but by different mechanisms. J Immunol 179:8035–8041, doi:179/12/8035

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work has been funded through the call Consolidation of Research Groups Basque Government (IT833-13). The authors would like to acknowledge and thank all the donors who participated in this study and the staff of centers that have collaborated in the project for their help in collecting samples. The authors are grateful to Maite Alvarez, Ph.D., for her technical and human support provided by the DNA Bank Service (SGIker) of the University of the Basque Country (UPV/EHU).

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. BIOMICs Research Group, Lascaray Research Center, University of the Basque Country UPV/EHU, Vitoria-Gasteiz, Spain

    N. G. Bediaga, J. M. Aznar, X. Elcoroaristizabal, O. Albóniga, Ana Rocandio & M. M. de Pancorbo

  2. Integral de Atención a Mayores (C.I.A.M.) “San Prudencio”, Center (CIAM) “San Prudencio”, Vitoria-Gasteiz, Spain

    F. Gómez-Busto

  3. Residencia y Unidad Sociosanitaria Orue, Amorebieta, Vizcaya, Spain

    I. Artaza Artabe

Authors
  1. N. G. Bediaga
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  2. J. M. Aznar
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  3. X. Elcoroaristizabal
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  4. O. Albóniga
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  5. F. Gómez-Busto
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  6. I. Artaza Artabe
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  7. Ana Rocandio
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  8. M. M. de Pancorbo
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Corresponding author

Correspondence to M. M. de Pancorbo.

Electronic supplementary material

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Table S1

Statistical power analysis of the study (DOC 44 kb)

Table S2

Allele frequency distribution for 21 autosomal STRs in nonagenarians (DOC 229 kb)

Table S3

Allele frequency distribution for 21 autosomal STRs in controls (DOC 250 kb)

Table S4

Comparison of allele frequencies using the chi-square test (DOC 70 kb)

Table S5

Genotypic frequencies of the HUMTHO1 STR across three different European populations (DOC 77 kb)

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Bediaga, N.G., Aznar, J.M., Elcoroaristizabal, X. et al. Associations between STR autosomal markers and longevity. AGE 37, 95 (2015). https://doi.org/10.1007/s11357-015-9818-5

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