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Association of CYP46 intron 2 polymorphism in Finnish Alzheimer’s disease samples and a global scale summary
  1. S Helisalmi1,
  2. S Vepsäläinen1,
  3. A M Koivisto1,
  4. A Mannermaa2,
  5. S Iivonen3,
  6. M Hiltunen3,
  7. V Kiviniemi4,
  8. H Soininen5
  1. 1Department of Neuroscience and Neurology, Univeristy Hospital and Brain Research Unit, Clinical Research Centre/Mediteknia, University of Kuopio, Kuopio, Finland
  2. 2Department of Clinical Pathology and Forensic Medicine, University of Kuopio, Kuopio, Finland
  3. 3Department of Neuroscience and Neurology, University Hospital and Brain Research Unit, Clinical Research Centre/Mediteknia, University of Kuopio, Kuopio, Finland
  4. 4Statistical and Mathematical Services, Information Technology Centre, University of Kuopio, Kuopio, Finland
  5. 5Department of Neuroscience and Neurology, University Hospital and Brain Research Unit, Clinical Research Centre/Mediteknia, University of Kuopio, Kuopio, Finland
  1. Correspondence to:
 S Helisalmi
 Department of Neuroscience and Neurology, University Hospital and University of Kuopio, Kuopio, Finland;seppo.helisalmi{at}uku.fi

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Cholesterol 24S-hydroxylase (CYP46; Gene ID: 10858) in chromosome 14q32.1 plays a key role in the hydroxylation of brain cholesterol to 24-hydroxycholesterol.1 This primary cholesterol elimination product can be transported through the blood-brain barrier. 24S-hydroxycholesterol is in in vitro conditions neurotoxic and may contribute to neurodegeneration.2

The gene for apolipoprotein E (APOE), a major cholesterol-transporting plasma protein, is expressed as three different polymorphic allelic forms (APOE ε2, ε3, and ε4) of which APOE ε4 is associated with an increased risk of Alzheimer’s disease (AD). A small amount of cholesterol exits via an APOE mediated pathway through the cerebrospinal fluid.1 Because depletion of brain cholesterol levels reduces the generation of β amyloid protein in the brain and cholesterol lowering drugs may reduce the risk of dementia,1 we tested the hypothesis that the previously examined single nucleotide polymorphism dbSNP:754203 in the CYP46 gene3 with or without the APOE ε4 allele was associated with AD in a Finnish population. Further, we performed a meta-analysis of the CYP46 dbSNP:754203 polymorphism using all reported findings of similar association studies on Medline (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi) up to April 2005 to evaluate the true global effect of the polymorphism as a susceptibility factor for AD.

The study population was examined in the Department of Neurology, Kuopio University Hospital.4 The ethical committee of University Hospital approved the study. The subjects consisted of 422 AD patients (mean age of onset 72±7 years; 293 (69%) women) and 469 controls (mean age at examination or death 70±5 years; 284 (61%) women), who …

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