A pilot study of gene/gene and gene/environment interactions in Alzheimer disease

Clin Med Res. 2011 Mar;9(1):17-25. doi: 10.3121/cmr.2010.894. Epub 2010 Aug 3.

Abstract

Background: Although some genes associated with increased risk of Alzheimer Disease (AD) have been identified, few data exist related to gene/gene and gene/environment risk of AD. The purpose of this pilot study was to explore gene/gene and gene/environment associations in AD and to obtain data for sample size estimates for larger, more definitive studies of AD.

Methods: The effect of gene/gene and gene/environment interaction related to late onset Alzheimer Disease (LOAD) was investigated in 153 subjects with LOAD and 302 gender matched controls enrolled in the Personalized Medicine Research Project, a population-based bio-repository. Genetic risk factors examined included APOE, ACE, OLR1,and CYP46 genes, and environmental factors included smoking, total cholesterol, LDL, HDL, triglycerides, C-reactive protein, blood pressure, statin use, and body mass index.

Results: The mean age of the cases was 78.2 years and the mean age of the controls was 87.2 years. APOE4 was significantly associated with LOAD (OR=3.55, 95%CL=1.70, 7.45). Cases were significantly more likely to have ever smoked cigarettes during their life (49.3% versus 38.4%, p=0.03). The highest recorded blood pressure and pulse pressure measurements were significantly higher in the controls than the cases (all P<0.005). Although not statistically significant in this pilot study, the relationship of the following factors was associated in opposite directions with LOAD based on the presence of an APOE4 allele: obesity at the age of 50, ACE, OLR1, and CYP46.

Conclusions: These pilot data suggest that gene/gene and gene/environment interactions may be important in LOAD, with APOE, a known risk factor for LOAD, affecting the relationship of ACE and OLR1 to LOAD. Replication with a larger sample size and in other racial/ethnic groups is warranted and the allele and risk factor frequencies will assist in choosing an appropriate sample size for a definitive study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / blood*
  • Alzheimer Disease / epidemiology
  • Alzheimer Disease / genetics*
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism
  • Blood Pressure
  • Body Mass Index
  • C-Reactive Protein / analysis
  • Cholesterol 24-Hydroxylase
  • Environment
  • Epistasis, Genetic*
  • Female
  • Humans
  • Lipoproteins, HDL / blood
  • Lipoproteins, LDL / blood
  • Male
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / metabolism
  • Pilot Projects
  • Risk Factors
  • Scavenger Receptors, Class E / genetics
  • Scavenger Receptors, Class E / metabolism
  • Smoking / blood
  • Smoking / epidemiology
  • Smoking / genetics
  • Steroid Hydroxylases / genetics
  • Steroid Hydroxylases / metabolism
  • Triglycerides / blood

Substances

  • Apolipoproteins E
  • Lipoproteins, HDL
  • Lipoproteins, LDL
  • OLR1 protein, human
  • Scavenger Receptors, Class E
  • Triglycerides
  • C-Reactive Protein
  • Steroid Hydroxylases
  • Cholesterol 24-Hydroxylase
  • ACE protein, human
  • Peptidyl-Dipeptidase A