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

Nader Ghebranious, Bickol Mukesh, Philip F. Giampietro, Ingrid Glurich, Susan F. Mickel, Stephen C. Waring, Catherine A. McCarty

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)17-25
Number of pages9
JournalClinical Medicine and Research
Volume9
Issue number1
DOIs
StatePublished - Mar 1 2011

Keywords

  • ACE
  • APOE
  • Alzheimer disease
  • Biobank
  • Body mass index
  • CYP46
  • Late onset
  • OLR1
  • Smoking

Fingerprint

Dive into the research topics of 'A pilot study of gene/gene and gene/environment interactions in Alzheimer disease'. Together they form a unique fingerprint.

Cite this