Neurobiology of Aging
Volume 31, Issue 9 , Pages 1563-1568 , September 2010

Polymorphisms in LMNA and near a SERPINA gene cluster are associated with cognitive function in older people

  • Christie Cluett

      Affiliations

    • Peninsula Medical School, RD&E Wonford Site, Barrack Road, Exeter EX2 5DW, UK
  • ,
  • Carol Brayne

      Affiliations

    • Department of Public Health & Primary Care, University Forvie Site, Robinson Way, Cambridge CB2 0SR, UK
  • ,
  • Robert Clarke

      Affiliations

    • Clinical Trial Service Unit, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK
  • ,
  • Grimley Evans

      Affiliations

    • Green College, Woodstock Road, Oxford OX2 6HE, UK
  • ,
  • Fiona Matthews

      Affiliations

    • MRC Biostatistics Unit, Institute of Public Health, Robinson Way, University Forvie Site, Cambridge CB2 0SR, UK
  • ,
  • David C. Rubinsztein

      Affiliations

    • Department of Medical Genetics, Cambridge Institute for Medical Research, Wellcome/MRC Building, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2XY, UK
  • ,
  • Felicia Huppert

      Affiliations

    • Academic Department of Psychiatry, Addenbrooke’s Hospital, Hills Road, Cambridge CB2 2XY, UK
  • ,
  • David J. Llewellyn

      Affiliations

    • Department of Public Health & Primary Care, University Forvie Site, Robinson Way, Cambridge CB2 0SR, UK
  • ,
  • Neil Rice

      Affiliations

    • Peninsula Medical School, RD&E Wonford Site, Barrack Road, Exeter EX2 5DW, UK
  • ,
  • William Henley

      Affiliations

    • Peninsula Medical School, RD&E Wonford Site, Barrack Road, Exeter EX2 5DW, UK
  • ,
  • Timothy M. Frayling

      Affiliations

    • Peninsula Medical School, RD&E Wonford Site, Barrack Road, Exeter EX2 5DW, UK
  • ,
  • Anna Murray

      Affiliations

    • Peninsula Medical School, RD&E Wonford Site, Barrack Road, Exeter EX2 5DW, UK
  • ,
  • David Melzer

      Affiliations

    • Peninsula Medical School, RD&E Wonford Site, Barrack Road, Exeter EX2 5DW, UK
    • Corresponding Author InformationCorresponding author. Tel.: +44 1392 406753; fax: +44 1392 406767.

Received 17 December 2007 ,Revised 5 June 2008 ,Accepted 29 August 2008.

References 

  1. Agrelo R, Setien F, Espada J, Artiga MJ, Rodriguez M, Perez-Rosado A, et al. Inactivation of the lamin A/C gene by CpG island promoter hypermethylation in hematologic malignancies, and its association with poor survival in nodal diffuse large B-cell lymphoma. J. Clin. Oncol. 2005;23:3940–3947
  2. Araujo-Vilar D, Lado-Abeal J, Palos-Paz F, Lattanzi G, Bandin MA, Bellido D, et al. A novel phenotypic expression associated with a new mutation in LMNA gene, characterized by partial lipodystrophy, insulin-resistance, aortic stenosis and hypertrophic cardiomyopathy. Clin. Endocrinol. (Oxf.). 2007;
  3. Baune BT, Ponath G, Rothermundt M, Riess O, Funke H, Berger K. Association between genetic variants of IL-1beta, IL-6 and TNF-alpha cytokines and cognitive performance in the elderly general population of the MEMO-study. Psychoneuroendocrinology. 2008;33:68–76
  4. Bennett C, Crawford F, Osborne A, Diaz P, Hoyne J, Lopez R, et al. Evidence that the APOE locus influences rate of disease progression in late onset familial Alzheimer’s Disease but is not causative. Am. J. Med. Genet. 1995;60:1–6
  5. Blacker D, Haines JL, Rodes L, Terwedow H, Go RC, Harrell LE, et al. ApoE-4 and age at onset of Alzheimer’s disease: the NIMH genetics initiative. Neurology. 1997;48:139–147
  6. Boucher DM, Schaffer M, Deissler K, Moore CA, Gold JD, Burdsal CA, et al. Goosecoid expression represses Brachyury in embryonic stem cells and affects craniofacial development in chimeric mice. Int. J. Dev. Biol. 2000;44:279–288
  7. Brayne C, Gao L, Dewey M, Matthews FE. Dementia before death in ageing societies—the promise of prevention and the reality. PLoS Med. 2006;3:e397
  8. Bridger JM, Foeger N, Kill IR, Herrmann H. The nuclear lamina. Both a structural framework and a platform for genome organization. FEBS J. 2007;274:1354–1361
  9. Cao H, Hegele RA. Nuclear lamin A/C R482Q mutation in Canadian kindreds with Dunnigan-type familial partial lipodystrophy. Hum. Mol. Genet. 2000;9:109–112
  10. Coon KD, Myers AJ, Craig DW, Webster JA, Pearson JV, Lince DH, et al. A high-density whole-genome association study reveals that APOE is the major susceptibility gene for sporadic late-onset Alzheimer’s disease. J. Clin. Psychiatry. 2007;68:613–618
  11. Daw EW, Payami H, Nemens EJ, Nochlin D, Bird TD, Schellenberg GD, et al. The number of trait loci in late-onset Alzheimer disease. Am. J. Hum. Genet. 2000;66:196–204
  12. Denecke J, Brune T, Feldhaus T, Robenek H, Kranz C, Auchus RJ, et al. A homozygous ZMPSTE24 null mutation in combination with a heterozygous mutation in the LMNA gene causes Hutchinson-Gilford progeria syndrome (HGPS): insights into the pathophysiology of HGPS. Hum. Mutat. 2006;27:524–531
  13. Duesing K, Charpentier G, Marre M, Tichet J, Hercberg S, Froguel P, et al. Evaluating the association of common LMNA variants with type 2 diabetes and quantitative metabolic phenotypes in French Europids. Diabetologia. 2008;51:76–81
  14. Farrer LA, Myers RH, Connor L, Cupples LA, Growdon JH. Segregation analysis reveals evidence of a major gene for Alzheimer disease. Am. J. Hum. Genet. 1991;48:1026–1033
  15. Grupe A, Abraham R, Li Y, Rowland C, Hollingworth P, Morgan A, et al. Evidence for novel susceptibility genes for late-onset Alzheimer’s disease from a genome-wide association study of putative functional variants. Hum. Mol. Genet. 2007;16:865–873
  16. Harris SE, Fox H, Wright AF, Hayward C, Starr JM, Whalley LJ, et al. A genetic association analysis of cognitive ability and cognitive ageing using 325 markers for 109 genes associated with oxidative stress or cognition. BMC Genet. 2007;8:43
  17. Hartwell KA, Muir B, Reinhardt F, Carpenter AE, Sgroi DC, Weinberg RA. The Spemann organizer gene, Goosecoid, promotes tumor metastasis. Proc. Natl. Acad. Sci. U.S.A. 2006;103:18969–18974
  18. Huang S, Risques RA, Martin GM, Rabinovitch PS, Oshima J. Accelerated telomere shortening and replicative senescence in human fibroblasts overexpressing mutant and wild-type lamin A. Exp. Cell Res. 2008;314:82–91
  19. McClearn GE, Johansson B, Berg S, Pedersen NL, Ahern F, Petrill SA, et al. Substantial genetic influence on cognitive abilities in twins 80 or more years old. Science. 1997;276:1560–1563
  20. McGue M, Christensen K. The heritability of cognitive functioning in very old adults: evidence from Danish twins aged 75 years and older. Psychol. Aging. 2001;16:272–280
  21. Moir RD, Spann TP. The structure and function of nuclear lamins: implications for disease. Cell Mol. Life Sci. 2001;58:1748–1757
  22. Raffaele Di Barletta M, Ricci E, Galluzzi G, Tonali P, Mora M, Morandi L, et al. Different mutations in the LMNA gene cause autosomal dominant and autosomal recessive Emery-Dreifuss muscular dystrophy. Am. J. Hum. Genet. 2000;66:1407–1412
  23. Rao VS, Cupples A, van Duijn CM, Kurz A, Green RC, Chui H, et al. Evidence for major gene inheritance of Alzheimer disease in families of patients with and without apolipoprotein E epsilon 4. Am. J. Hum. Genet. 1996;59:664–675
  24. Rubinsztein DC, Easton DF. Apolipoprotein E genetic variation and Alzheimer’s disease: a meta-analysis. Dement. Geriatr. Cogn. Disord. 1999;10:199–209
  25. Schaefer JS, Zhang M. Role of maspin in tumor metastasis and angiogenesis. Curr. Mol. Med. 2003;3:653–658
  26. Seshadri S, DeStefano AL, Au R, Massaro JM, Beiser AS, Kelly-Hayes M, et al. Genetic correlates of brain aging on MRI and cognitive test measures: a genome-wide association and linkage analysis in the Framingham Study. BMC Med. Genet. 2007;8(Suppl. 1):S15
  27. Shams TM, Samaka RM, Shams ME. Maspin protein expression: a special feature of papillary thyroid carcinoma. J. Egypt Natl. Canc. Inst. 2006;18:274–280
  28. Sharpless NE, DePinho RA. How stem cells age and why this makes us grow old. Nat. Rev. Mol. Cell Biol. 2007;8:703–713
  29. Slooter AJ, Cruts M, Kalmijn S, Hofman A, Breteler MM, Van Broeckhoven C, et al. Risk estimates of dementia by apolipoprotein E genotypes from a population-based incidence study: the Rotterdam Study. Arch. Neurol. 1998;55:964–968
  30. Swan GE, Carmelli D, Reed T, Harshfield GA, Fabsitz RR, Eslinger PJ. Heritability of cognitive performance in aging twins. The National Heart, Lung, and Blood Institute Twin Study. Arch. Neurol. 1990;47:259–262
  31. Yaffe K, Lindquist K, Sen S, Cauley J, Ferrell R, Penninx B, et al. Estrogen receptor genotype and risk of cognitive impairment in elders: findings from the Health ABC study. Neurobiol. Aging. 2007;
  32. Yip AG, Brayne C, Easton D, Rubinsztein DC. Apolipoprotein E4 is only a weak predictor of dementia and cognitive decline in the general population. J. Med. Genet. 2002;39:639–643

PII: S0197-4580(08)00323-0

doi: 10.1016/j.neurobiolaging.2008.08.020

Neurobiology of Aging
Volume 31, Issue 9 , Pages 1563-1568 , September 2010