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- Title
A Pilot Study of Gene/Gene and Gene/Environment Interactions in Alzheimer Disease.
- Authors
Ghebranious, Nader; Mukesh, Bickol; Giampietro, Philip F.; Gluhch, Ingrid; Michel, Susan F.; Waring, Stephen C.; McCarty, Catherine A.
- 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.
- Subjects
WISCONSIN; GENETICS of Alzheimer's disease; ALZHEIMER'S disease risk factors; ALZHEIMER'S disease; ANALYSIS of variance; APOLIPOPROTEINS; CHI-squared test; COMPUTER software; CONFIDENCE intervals; EPIDEMIOLOGY; GENES; POLYMERASE chain reaction; RESEARCH funding; STATISTICS; T-test (Statistics); PHENOTYPES; LOGISTIC regression analysis; SAMPLE size (Statistics); PILOT projects; DATA analysis; CASE-control method
- Publication
Clinical Medicine & Research, 2011, Vol 9, Issue 1, p17
- ISSN
1539-4182
- Publication type
Article
- DOI
10.3121/cmr.2010.894