A functional polymorphism in the HMGCR promoter affects transcriptional activity but not the risk for Alzheimer disease in Swedish populations

作者：Keller Lina^*; Murphy Charlotte; Wang Hui Xin; Fratiglioni Laura; Olin Maria; Gafvels Mats; Bjorkhem Ingemar; Graff Caroline; Meaney Steve

来源：Brain Research, 2010, 1344: 185-191.

DOI：10.1016/j.brainres.2010.04.073

• Alzheimer disease
• Single nucleotide polymorphism
• HMGCR
• Promoter activity
• Genetic association
• Cholesterol

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 hydroxymethyl-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).

• 出版日期2010-7-16