Journal of Neurology

, Volume 255, Issue 5, pp 668–673

Genetic study between SIRT1, PPARD, PGC-1α genes and Alzheimer’s disease

  • S. Helisalmi
  • S. Vepsäläinen
  • M. Hiltunen
  • A. M. Koivisto
  • A. Salminen
  • M. Laakso
  • H. Soininen
ORIGINAL COMMUNICATION
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Abstract

Single nucleotide polymorphisms (SNPs) in three diabetes-related genes (SIRT1, PPARD, PGC-1α) were investigated with a case-control approach. To examine the genetic association of those genes with Alzheimer’s disease (AD) risk, we used the TaqMan technique to genotype five SNP sites for SIRT1, six for PPARD and eight for the PGC-1α gene, in 326 Finnish AD cases and 463 controls and conducted a single allele and genotypic distribution comparison as well as estimated haplotype frequencies between cases and controls. No significant differences in AD risk were found in single SNP and haplotype analyses for any of the three genes between 326 cases and 463 controls. However, in a subgroup of women older than 65 years, the frequencies of three SNPs in the SIRT1 gene were significantly different between AD and controls. We conclude that there is no real association with SNPs available in the present study between SIRT1, PPARD or PGC-1α genes and AD risk in the Finnish population.

Key words

Alzheimer’s disease diabetes linkage disequilibrium SNP haplotype 

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References

  1. 1.
    Anekonda TS, Reddy PH (2006) Neuronal protection by sirtuins in Alzheimer’s disease. J Neurochem 96:305–313PubMedCrossRefGoogle Scholar
  2. 2.
    Blander G, Guarente L (2004) The Sir2 family of protein deacetylases. Annu Rev Biochem 73:417–435PubMedCrossRefGoogle Scholar
  3. 3.
    Corton JC, Brown-Borg HM (2005) Peroxisome proliferator-activated receptor gamma coactivator 1 in caloric restriction and other models of longevity. J Gerontol A Biol Sci Med Sci 60(12):1494–1509PubMedGoogle Scholar
  4. 4.
    Finck BN, Kelly DP (2006) PGC-1 coactivators: inducible regulators of energy metabolism in health and disease. J Clin Invest 116:615–622PubMedCrossRefGoogle Scholar
  5. 5.
    Gerhart-Hines Z, Rodgers JT, Bare O, Lerin C, Kim SH, Mostoslavsky R, Alt FW, Wu Z, Puigserver P (2007) Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1 alpha. EMBO 26(7):1913–1923CrossRefGoogle Scholar
  6. 6.
    Holzapfel J, Heun R, Lütjohann D, Jessen F, Maier W, Kölsch H (2006) PPARD haplotype influences cholesterol metabolism but is no risk factor of Alzheimer’s disease. Neurosci Lett 408:57–61PubMedCrossRefGoogle Scholar
  7. 7.
    The international HapMap consortium (2003) The international HapMap project. Nature 426(6968):789–796CrossRefGoogle Scholar
  8. 8.
    Lacquemant C, Chikri M, Boutin P, Samson C, Froquel P (2002) No association between the G482S polymorphism of the proliferator-activated receptor-gamma coactivator-1 (PGC-1) gene and Type II diabetes in French Caucasians. Diabetologia 45(4):602–603PubMedCrossRefGoogle Scholar
  9. 9.
    Lagouge M, Argmann C, Gerhart- Hines Z, Meziane H, Lerin C, Daussin F, Messadeq N, Milne J, Lambert P, Elliott P, Geny B, Laakso M, Puigserver P, Auwerx J (2006) Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1α. Cell 127:1109–1122PubMedCrossRefGoogle Scholar
  10. 10.
    Mattson MP (2003) Will caloric restriction and folate protect against AD and PD? Neurology 60:690–695PubMedCrossRefGoogle Scholar
  11. 11.
    McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS-ADRDA work group under the auspices of department of health and human services task force on Alzheimer’s disease. Neurology 34:939–944PubMedGoogle Scholar
  12. 12.
    Morgan AR, Turic D, Jehu L, Hamilton G, Hollingworth P, Moskvina V, Jones L, Lovestone S, Brayne C, Rubinsztein DC, Lawlor B, Gill M, O’Donovan MC, Owen MJ, Williams J (2007) Association studies of 23 positional/functional candidate genes on chromosome 10 in late-onset Alzheimer’s disease. Am J Med Genet B Neuropsychiatr Genet 144(6):762–770Google Scholar
  13. 13.
    Muller YL, Bogardus C, Pedersen O, Baier L (2003) A Gly482Ser missense mutation in the peroxisome proliferator-activated receptor gamma coactivator-1 is associated with altered lipid oxidation and early insulin secretion in Pima Indians. Diabetes 52(3):895–898PubMedCrossRefGoogle Scholar
  14. 14.
    Ott A, Stolk RP, van Harskamp F, Pols HA, Hofman A, Breteler MM (1999) Diabetes mellitus and the risk of dementia: the Rotterdam study. Neurology 53:1937–1942PubMedGoogle Scholar
  15. 15.
    Pasquier F, Boulogne A, Leys D, Fontaine P (2006) Diabetes mellitus and dementia. Diabetes metab 32:403–414PubMedCrossRefGoogle Scholar
  16. 16.
    Pihlajamäki J, Kinnunen M, Ruotsalainen E, Salmenniemi U, Vauhkonen I, Kuulasmaa T, Kainulainen S, Laakso M (2005) Haplotypes of PPARGC1A are associated with glucose tolerance, body mass index and insulin sensitivity in offspring of patients with type 2 diabetes. Diabetologia 48:1331–1334PubMedCrossRefGoogle Scholar
  17. 17.
    Purcell S, Cherney SS, Sham PC (2003) Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits. Bioinformatics 19:149–150PubMedCrossRefGoogle Scholar
  18. 18.
    Qin W, Yang T, Ho L, Zhao Z, Wang J, Chen L, Zhao W, Thiyagarajan M, MacGrogan D, Rodgers JT, Puigserver P, Sadoshima J, Deng H, Redrini S, Gandy S, Sauve AA, Pasinetti GM (2006) Neuronal SIRT1 activation as a novel mechanism underlying the prevention of Alzheimer disease amyloid neuropathology by caloric restriction. J Biol Chem 281:21745–21754PubMedCrossRefGoogle Scholar
  19. 19.
    Rodgers JT, Lerin C, Haas W, Gygi SP, Spiegelman BM, Puigserver P (2005) Nutrient control of glucose homeostasis through a complex of PGC-1 alpha and SIRT1. Nature 434:113–118PubMedCrossRefGoogle Scholar
  20. 20.
    Sinclair DA (2005) Toward a unified theory of caloric restriction and longevity regulation. Mech Ageing Dev 126:987–1002PubMedCrossRefGoogle Scholar
  21. 21.
    Skogsberg J, McMahon AD, Karpe F, Hamsten A, Packard CJ, Ehrenborg E, West of Scotland Coronary Prevention Study (2003) Peroxisome proliferator activated receptor delta genotype in relation to cardiovascular risk factors and risk of coronary heart disease in hypercholesterolaemic men. J Intern Med 254(6):597–604PubMedCrossRefGoogle Scholar
  22. 22.
    Stumvoll M, Fritsche A, t’Hart LM, Machann J, Thamer C, Tschritter O, Van Haeften TW, Jacob S, Dekker JM, Maassen JA, Machicao F, Schick F, Heine RJ, Haring H (2004) The Gly482Ser variant in the peroxisome proliferator-activated receptor gamma coactivator-1 is not associated with diabetes-related traits in non-diabetic German and Dutch populations. Exp Clin Endocrinol Diabetes 112(5):253–257PubMedCrossRefGoogle Scholar
  23. 23.
    Tsukamoto K, Watanabe T, Matsushima T, Kinoshita M, Kato H, Hashimoto Y, Kurokawa K and Teramoto T (1993) Determination by PCR_RFLP of apoe genotype in a Japanese population. J Lab Clin Med 121:598–602PubMedGoogle Scholar
  24. 24.
    Valerio A, Boroni F, Sarnica I, Ghisi V, Bresciani LG, Ferrario M, Borsani G, Spano P, Pizzi M. NF-kappaB pathway: a target for preventing beta-amyloid (Aβ)-induced neuronal damage and Abeta42 production (2006) Eur J Neurosci 23:1711–1720PubMedCrossRefGoogle Scholar
  25. 25.
    Vänttinen M, Nuutila P, Kuulasmaa T, Pihlajamäki J, Hällsten K, Virtanen KA, Lautamäki R, Peltoniemi P, Takala T, Viljanen APM, Knuuti J, Laakso M (2005) Single nucleotide polymorphisms in the peroxisome proliferator-activated receptor δ gene are associated with skeletal muscle glucose uptake. Diabetes 54:3587–3591PubMedCrossRefGoogle Scholar
  26. 26.
    Wang YX, Lee CH, Tiep S, Yu RT, Ham J, Kang H, Evans RM (2003) Peroxisome- proliferator-activated receptor δ activates fat metabolism to prevent obesity. Cell 113:159–170PubMedCrossRefGoogle Scholar

Copyright information

© Steinkopff-Verlag 2008

Authors and Affiliations

  • S. Helisalmi
    • 1
  • S. Vepsäläinen
    • 1
  • M. Hiltunen
    • 1
  • A. M. Koivisto
    • 1
  • A. Salminen
    • 1
  • M. Laakso
    • 3
  • H. Soininen
    • 1
    • 2
  1. 1.Institute of Clinical Medicine, Unit of Neurology and Brain Research UnitClinical Research Center, Mediteknia, Kuopio UniversityKuopioFinland
  2. 2.Dept. of NeurologyKuopio University HospitalKuopioFinland
  3. 3.Dept. of MedicineKuopio University and University HospitalKuopioFinland

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