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A Functional Polymorphism In The Hmgcr Promoter Affects Transcriptional Activity But Not The Risk For Alzheimer Disease In Swedish Populations
Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
Stockholm University, Faculty of Social Sciences, Aging Research Center (ARC), (together with KI).
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2010 (English)In: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1344, 185-91 p.Article in journal (Refereed) Published
Abstract [en]

Variations in genes associated with cholesterol homeostasis have been reported to modify the risk of developing Alzheimer disease (AD). To date there have been few investigations into variations in genes directly involved in cholesterol biosynthesis and AD. We investigated the influence of the -911C>A polymorphism (rs3761740) in the hydroxy-methyl-glutaryl CoA reductase (HMGCR) gene promoter on basal and regulated transcription, plasma cholesterol levels and the association with AD. Under in vitro conditions the A allele was found to be significantly more responsive to SREBP-2 mediated regulation than the C allele. In an age and sex matched case-control study, the genotype distribution and allele frequency of this polymorphism were not associated with AD (OR=1.03; 95% CI=0.72-1.48). However, we did find evidence supporting an interaction between the HMGCR A allele, the APOE E4 allele and an altered risk of AD (OR=2.41; 95% CI=0.93-6.22).

Place, publisher, year, edition, pages
Amsterdam: Elsevier, 2010. Vol. 1344, 185-91 p.
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Public Health, Global Health, Social Medicine and Epidemiology
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URN: urn:nbn:se:su:diva-85138DOI: 10.1016/j.brainres.2010.04.073PubMedID: 20450896OAI: oai:DiVA.org:su-85138DiVA: diva2:585445
Available from: 2013-01-10 Created: 2013-01-07 Last updated: 2017-12-06Bibliographically approved

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