Literature DB >> 30975575

Association study of rs3846662 with Alzheimer's disease in a population-based cohort: the Cache County Study.

Sage M Wright1, Samantha L Jensen1, Kristen L Cockriel1, Brian Davis1, JoAnn T Tschanz2, Ronald G Munger3, Christopher D Corcoran4, John S K Kauwe5.   

Abstract

3-Hydroxy-3-methylglutaryl coenzyme A reductase is associated with monitoring cholesterol levels. The presence of the single-nucleotide polymorphism rs3846662 introduces alternative splicing at exon 13; the exclusion of this exon leads to a reduction in total cholesterol levels. Lower cholesterol levels are linked to a reduction in Alzheimer's disease (AD) risk. The major allele of rs3846662, which encourages the splicing of exon 13, has recently been shown to act as a preventative allele for AD, especially in women. The purpose of our research was to replicate and confirm this finding. Using logistic regressions and survival curves, we found a significant association between AD and rs3846662, with a stronger association in individuals who carry the APOE e4 allele, supporting previously published work. The effect of rs3846662 on women is insignificant in our cohort. We confirmed that rs3846662 is associated with reduced risk for AD without gender differences; however, we failed to detect association between rs3846662 and delayed mild cognitive impairment conversion to AD for either of the APOE e4 allelic groups.
Copyright © 2019 Elsevier Inc. All rights reserved.

Entities:  

Keywords:  APOE; Alzheimer's disease; Association; Cholesterol synthesis; Genetics; HMGCR

Year:  2019        PMID: 30975575      PMCID: PMC6745283          DOI: 10.1016/j.neurobiolaging.2019.03.004

Source DB:  PubMed          Journal:  Neurobiol Aging        ISSN: 0197-4580            Impact factor:   4.673


  30 in total

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