Skip to main content

Advertisement

SpringerLink
Log in

Association of CETP polymorphisms with the risk of vascular dementia and white matter lesions

  • Dementias - Original Article
  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Abstract

Cholesteryl ester transfer protein (CETP), a component of the high density lipoprotein (HDL), plays a central role in reverse cholesterol transport. We investigated the association of two putative functional CETP polymorphisms (C-629A and I405V) with the risk of vascular dementia (VD) and tested if this association is influenced by the presence of APOE4 allele. Our study included 163 VD patients (mean age: 74.25 ± 7.9 years) and 452 cognitively healthy probands (mean age: 70.81 ± 7.9 years). As a biological correlate, the association of CETP gene variants with white matter lesion (WML) load was investigated. Neither the C-629A (P = 0.169) nor the I405V (P = 0.840) polymorphism was associated with VD risk in the whole sample. However, in non-carriers of the APOE4 allele, homozygote carriers of the CETP C-629A A allele presented with an increased risk of VD (P = 0.01). Whereas in APOE4 carriers, no association of CETP polymorphisms with VD risk was detected. In addition, carriers of the CETP C-629A AA genotype presented with decreased WML load in the frontal brain (P = 0.009). Our results suggest that CETP gene polymorphisms might influence WML load and the risk of VD, the latter in non-carriers of the APOE4 allele.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Alberts MJ (2003) Stroke genetics update. Stroke 34:342–344

    Article  PubMed  Google Scholar 

  • Altamura C, Squitti R, Pasqualetti P, Tibuzzi F, Silvestrini M, Ventriglia MC, Cassetta E, Rossini PM, Vernieri F (2007) What is the relationship among atherosclerosis markers, apolipoprotein E polymorphism and dementia? Eur J Neurol 14:679–682

    Article  PubMed  CAS  Google Scholar 

  • Arias-Vasquez A, Isaacs A, Aulchenko YS, Hofman A, Oostra BA, Breteler M, van Dujin CM (2007) The cholesteryl ester transfer protein (CETP) gene and the risk of Alzheimer’s disease. Neurogenetics 8:189–193

    Article  PubMed  CAS  Google Scholar 

  • Baum L, Lam LC, Kwok T, Lee J, Chiu HF, Mok VC, Wong A, Chen X, Cheung WS, Pang CP, Ma SL, Tang NL, Wong KS, Ng HK (2006) Apolipoprotein E epsilon4 allele is associated with vascular dementia. Dement Geriatr Cogn Disord 22:301–305

    Article  PubMed  CAS  Google Scholar 

  • Bruce C, Sharp DS, Tall AR (1998) Relationship of HDL and coronary heart disease to a common amino acid polymorphism in the cholesteryl ester transfer protein in men with and without hypertriglyceridemia. J Lipid Res 39:1071–1078

    PubMed  CAS  Google Scholar 

  • Dachet C, Poirier O, Cambien F, Chapman J, Rouis M (2000) New functional promotor polymorphism, CETP/–629, in cholesteryl ester transfer protein (CETP) gene related to CETP mass and high density lipoprotein cholesterol levels (Role of SP1/Sp3 in transcriptional regulation). Aterioscler Thromb Vasc Biol 20:507–515

    CAS  Google Scholar 

  • Davidson Y, Gibbons L, Purandare N, Byme J, Hardicre J, Wren J, Payton A, Pendleton N, Horan M, Bums A, Mann DM (2006) Apolipoprotein E epsilon4 allele frequency in vascular dementia. Dement Geriatr Cogn Disord 22:15–19

    Article  PubMed  CAS  Google Scholar 

  • Dullaart RP, Borggreve SE, Hillege HL, Dallinga-Thie GM (2008) The association of HDL cholesterol concentration with the −629C>A CETP promoter polymorphism is not fully explained by its relationship with plasma cholesteryl ester transfer. Scand J Clin Lab Invest 68:99–105

    Article  PubMed  CAS  Google Scholar 

  • Englund E (2002) Neuropathology of white matter lesions in vascular cognitive impairment. Cerbrovasc Dis 13:11–15

    Article  Google Scholar 

  • Fidani L, Goulas A, Crook R, Petersen RC, Tangalos E, Kotsis A, Hardy J (2004) An onset association study of the cholesteryl ester transfer protein TaqI B polymorphism with late Alzheimer’s disease. Neurosci Lett 357:152–154

    Article  PubMed  CAS  Google Scholar 

  • Folstein MF, Folstein SE, McHugh PR, Mini-mental state (1975) A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198

    Article  PubMed  CAS  Google Scholar 

  • Frisdal E, Klerkx AH, Goff Le, Tanck MW, Lagarde JP, Jukema JW, Kastelein JJ, Chapman MJ, Guerin M (2005) Functional interaction between −629C/A, −971G/A and −1337C/T polymorphisms in the CETP gene is a major determinant of promoter activity and plasma CETP. Hum Mol Genet 14:2607–2618

    Article  PubMed  CAS  Google Scholar 

  • Hamilton G, Proitsi P, Jehu L, Morgan A, Williams J, O’Donovan MC, Owen MJ, Powell JF, Lovestone S (2007) Candidate gene association study of insulin signalling genes and Alzheimer’s disease: evidence for SOS2, PCK1, and PPAR gamma as susceptibility loci. Am J Med Genet B Neuropsychiatr Genet 144:508–516

    Google Scholar 

  • Hentschel F, Kreis M, Damian M, Diepers M, Disqué C, Dzialowski I, Kitzler H, Rodewald A, Struffert T, Trittmacher S, Wille PR (2005a) Reliability of quantifying vascular white matter brain lesions—a contribution to reproducible quantitative diagnosis. Rofo 177:105–113

    PubMed  CAS  Google Scholar 

  • Hentschel F, Kreis M, Damian M, Krumm B, Frölich L (2005b) The clinical utility of structural neuroimaging with MRI for diagnosis and differential diagnosis of dementia: a memory clinic study. Int J Geriatr Psychiatry 20:645–650

    Article  PubMed  CAS  Google Scholar 

  • Hentschel F, Damian M, Krumm B, Froelich L (2007) White matter lesions—age adjusted values for cognitively healthy and demented subjects. Acta Neurol Scan 115:74–80

    Google Scholar 

  • Hixson JE, Vernier DT (1990) Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res 31:545–548

    PubMed  CAS  Google Scholar 

  • Jellinger KH (2008) Morphologic diagnosis of “vascular dementia”—a critical update. J Neurol Sci 270:1–12

    Article  PubMed  Google Scholar 

  • Kölsch H, Linnebank M, Lütjohann D, Jessen F, Wüllner U, Harbrecht U, Thelen KM, Kreis M, Hentschel F, Schulz A, von Bergmann K, Maier W, Heun R (2004) Polymorphisms in glutathione S-transferase omega-1 and AD, vascular dementia, and stroke. Neurology 63:2255–2260

    PubMed  Google Scholar 

  • Kölsch H, Jessen F, Freymann N, Kreis M, Hentschel F, Maier W, Heun R (2005) ACE I/D polymorphism is a risk factor of Alzheimer’s disease but not of vascular dementia. Neurosci Lett 377:37–39

    Article  PubMed  Google Scholar 

  • Laurin D, Masaki KH, White LR, Launer LJ (2007) Ankle-to-brachial index and dementia: the Honolulu-Asia age study. Circulation 116:2269–2274

    Article  PubMed  Google Scholar 

  • Liao D, Cooper L, Cai J, Toole JF, Bryan NR, Hutchinson RG, Tyroler HA (1996) Presence and severity of cerebral white matter lesions and hypertension, its treatment and control. The Aric study. Atherosclerosis risk in Communities Study. Stroke 27:2262–2270

    PubMed  CAS  Google Scholar 

  • Lobo A, Launer LJ, Fratiglioni L, Andersen K, Di Carlo A, Breteler MM, Copeland JR, Dartigues JF, Jagger C, Martinez-Lage J, Soininen H, Hofman A (2000) Prevalence of dementia and major subtypes in Europe: a collaborative study of population-based cohorts. Neurologic diseases in the elderly research group. Neurology 54:10–15

    Google Scholar 

  • Miller AL (2003) The methionine-homocysteine cycle and its effects on cognitive diseases. Altern Med Rev 8:7–19

    PubMed  Google Scholar 

  • Moton RE, Greene DJ (2007) Partial suppression of CETP activity beneficially modifies the lipid transfer profile of plasma. Atherosclerosis 192:100–107

    Article  Google Scholar 

  • Oelsen OF, Dage L (2000) High density lipoprotein inhibits assembly of amyloid beta-peptide. Biochem Biophys Res Commun 270:62–66

    Article  Google Scholar 

  • Rodríguez E, Mateo I, Infante J, Llorca J, Berciano J, Combarros O (2006) Cholesteryl ester transfer protein (CETP) polymorphism modifies the Alzheimer’s disease risk associated with APOE4 allele. J Neurol 253:181–185

    Article  PubMed  Google Scholar 

  • Stoppe G, Staedt J, Bruhn H (1995) Patchy changes in white matter in cranial computerized and magnetic resonance tomography—significance for (differential) diagnosis of dementia of the Alzheimer type and the vascular dementia. Fortschr Neurol Psychiatr 63:425–440

    Article  PubMed  CAS  Google Scholar 

  • Tall AR (1993) Plasma cholestery ester transfer protein. J Lipid Res 34:1255–1274

    PubMed  CAS  Google Scholar 

  • Thompson JF, Lira ME, Durham LK, Clark RW, Bamberger MJ, Milos PM (2003) Polymorphisms in the CETP gene and association with CETP mass and HDL levels. Atherosclerosis 167:195–204

    Article  PubMed  CAS  Google Scholar 

  • van Dijk EJ, Prins ND, Vermeer SE, Hofman A, van Duijn CM, Koudstaal PJ, Breteler MM (2004) Plasma amyloid beta, apolipoprotein E, lacunar infarcts, and white matter lesions. Ann Neurol 55:570–575

    Article  PubMed  Google Scholar 

  • Yamashita S, Hirano K, Sakai N, Matsuzawa Y (2000) Molecular biology and pathophysiological aspects of plasma CETP. Biochim Biophys Acta 1529:257–275

    PubMed  CAS  Google Scholar 

  • Zhu H, Gopalraj RK, Kelly JF, Bennett DA, Estus S (2005) Lack of genetic association of cholesteryl ester transfer protein polymorphisms with late onset Alzheimer’s disease. Neurosci Lett 381:36–41

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We thank Christine Ledschbor-Frahnert and Mihaela Keller for skilful technical assistance. This work was supported by grants from the AFI (AFI #03802), the DFG (He 2748/5 and KO2327/2-1) and by the BMBF within the framework of the Competence Network Dementia (grant: 01GI0422) and the competence Network Degenerative Dementia (grant: 01GI0711).

Author information

Authors and Affiliations

  1. Department of Psychiatry, University of Bonn, Sigmund-Freud-Straße 25, 53105, Bonn, Germany

    H. Qureischie, J. Popp, F. Jessen, W. Maier, S. Schmitz & H. Kölsch

  2. Division of Neuroscience, University of Birmingham, Birmingham, B15 2QZ, UK

    R. Heun

  3. Department of Neuroradiology, Faculty of Clinical Medicine Mannheim, Central Institute of Mental Health, University of Heidelberg J5, 68159, Mannheim, Germany

    F. Hentschel & P. Kelemen

Authors
  1. H. Qureischie
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. Heun
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. Popp
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. F. Jessen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. W. Maier
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S. Schmitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. F. Hentschel
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. P. Kelemen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. H. Kölsch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H. Kölsch.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Qureischie, H., Heun, R., Popp, J. et al. Association of CETP polymorphisms with the risk of vascular dementia and white matter lesions. J Neural Transm 116, 467–472 (2009). https://doi.org/10.1007/s00702-008-0180-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00702-008-0180-y

Keywords

Search

Navigation