Alpha-2-macroglobulin gene, oxidized low-density lipoprotein receptor-1 locus, and sporadic Alzheimer's disease

Neurobiol Aging. 2009 Sep;30(9):1518-20. doi: 10.1016/j.neurobiolaging.2007.11.015. Epub 2008 Jan 10.

Abstract

A total sample of 169 AD patients, and 264 age- and sex-matched unrelated caregivers from Apulia, southern Italy, were genotypized for alpha-2-macroglobulin (A2M) Val1000/Ile single-nucleotide polymorphism (SNP) (rs669), apolipoprotein E (APOE), and SNPs (+1073 and +1071) in the oxidized low-density lipoprotein receptor-1 (OLR1) gene on chromosome 12. A2M allele and genotype frequencies were similar between AD patients and controls, also after stratification for late onset (>/=70 years) and early onset (<70 years) or APOE varepsilon4 status. However, there was evidence in support of LD between the OLR1+1071, the OLR1+1073, and the rs669 SNPs, with T-C-A haplotype being associated with significant increased risk of AD in both the whole sample and when we stratified according to early and late onset AD subjects, with the allelic association with AD predominantly from the OLR1+1073 SNP, further supporting the role of OLR1 as a candidate risk gene for sporadic AD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / physiopathology
  • Apolipoprotein E4 / genetics
  • Brain / metabolism*
  • Brain / physiopathology
  • Chromosomes, Human, Pair 12 / genetics
  • Cohort Studies
  • DNA Mutational Analysis
  • Female
  • Gene Frequency / genetics
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing
  • Genotype
  • Haplotypes / genetics
  • Humans
  • Male
  • Middle Aged
  • Mutation / genetics
  • Nociceptin Receptor
  • Polymorphism, Genetic / genetics
  • Receptors, Opioid / genetics*
  • Risk Factors
  • alpha-Macroglobulins / genetics*

Substances

  • Apolipoprotein E4
  • Receptors, Opioid
  • alpha-Macroglobulins
  • Nociceptin Receptor
  • OPRL1 protein, human