Faster progression from MCI to probable AD for carriers of a single-nucleotide polymorphism associated with type 2 diabetes

Neurobiol Aging. 2018 Apr;64:157.e11-157.e17. doi: 10.1016/j.neurobiolaging.2017.11.013. Epub 2017 Dec 7.

Abstract

Sporadic Alzheimer's disease (AD), as opposed to its autosomal dominant form, is likely caused by a complex interaction of genetic, environmental, and health lifestyle factors. Twin studies indicate that sporadic AD heritability could be between 58% and 79%, around half of which is explained by the ε4 allele of the apolipoprotein E (APOE4). We hypothesized that genes associated with known risk factors for AD, namely hypertension, hypercholesterolemia, obesity, diabetes, and cardiovascular disease, would contribute significantly to the remaining heritability. We analyzed 22 AD-associated single-nucleotide polymorphisms (SNPs), associated with these risk factors, that were included in the sequencing data of the Alzheimer's Disease Neuroimaging Initiative 1 data set, which included 355 participants with mild cognitive impairment (MCI). We built survival models with the selected SNPs to predict progression of MCI to probable AD over the 10-year follow-up of the study. The rs391300 SNP, located on the serine racemase (SRR) gene and linked to increased susceptibility to type 2 diabetes, was associated with progression from MCI to probable AD.

Keywords: Alzheimer's disease; Genotype; Mild cognitive impairment; SRR gene; Type 2 diabetes; rs391300.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / genetics*
  • Cognitive Dysfunction / genetics*
  • Diabetes Mellitus, Type 2 / genetics*
  • Disease Progression
  • Female
  • Gene-Environment Interaction
  • Genetic Association Studies
  • Genetic Predisposition to Disease / genetics
  • Heterozygote*
  • Humans
  • Life Style
  • Male
  • Polymorphism, Single Nucleotide / genetics*
  • Racemases and Epimerases / genetics*
  • Risk Factors
  • Time Factors

Substances

  • Racemases and Epimerases
  • serine racemase