ArticleMolecular neurodegeneration2011
Evaluation of the global association between cholesterol-associated polymorphisms and Alzheimer's disease suggests a role for rs3846662 and HMGCR splicing in disease risk.
Article in Molecular neurodegeneration, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Multivariate Genome-Wide Association Analysis Identifies Genetic Susceptibility Loci for Metabolic Syndrome in the Korean Genome and Epidemiology Study.International journal of molecular sciences · 2026Article
- Review
- Association study of rs3846662 with Alzheimer's disease in a population-based cohort: the Cache County Study.Neurobiology of aging · 2019Article
- Article
- Pleiotropic association of LIPC variants with lipid and urinary 8-hydroxy deoxyguanosine levels in a Taiwanese population.Lipids in health and disease · 2019Article
- Association of theInternational journal of clinical and experimental pathology · 2018Article
- Association of HMGCR polymorphism with late-onset Alzheimer's disease in Han Chinese.Oncotarget · 2016Article
- Effect of HMGCR genetic variation on neuroimaging biomarkers in healthy, mild cognitive impairment and Alzheimer's disease cohorts.Oncotarget · 2016Article
- Effects of rs3846662 Variants on HMGCR mRNA and Protein Levels and on Markers of Alzheimer's Disease Pathology.Journal of molecular neuroscience : MN · 2016Article
- Regulation of SIRT1 by oxidative stress-responsive miRNAs and a systematic approach to identify its role in the endothelium.Antioxidants & redox signaling · 2013Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundRecent genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNP)s that are essentially unequivocally associated with peripheral cholesterol. Since the alleles of the APOE gene, which modulate peripheral cholesterol metabolism, and midlife plasma cholesterol are both associated with Alzheimer's disease (AD) risk, we have evaluated the hypothesis that SNPs associated with plasma cholesterol are also associated with AD.
resultsSeventeen non-APOE SNPs reproducibly associated with cholesterol per GWAS were tested for association with AD in ~2,000 AD and ~4,000 non-AD subjects. As a group, these SNPs are associated with AD. Two SNPs in particular, rs3846662 and rs1532085, are associated with AD risk and age-of-onset. Additionally, rs3846662 was associated with HMGCR exon 13 splicing in human liver but not brain, possibly obscured by CNS cell-type heterogeneity. However, rs3846662 was associated with HMGCR exon 13 splicing in liver- and brain-derived cell lines.
conclusionsCholesterol-associated SNPs outside of APOE confer a global risk for AD. Rs3846662 and rs1532085 are associated with both AD risk and age-of-onset. Rs3846662 is associated with HMGCR exon 13 inclusion. Since rs3846662 affects AD risk and age-of-onset as well as statin responsiveness, this SNP may confound clinical trials evaluating the protective effects of statins on AD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.