title: A pilot study of gene/gene and gene/environment interactions in Alzheimer disease.
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.
authors.affiliation: Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, WI 54449, USA.
authors.forename: Nader
authors.initials: N
authors.lastname: Ghebranious
authors.forename: Bickol
authors.initials: B
authors.lastname: Mukesh
authors.forename: Philip F
authors.initials: PF
authors.lastname: Giampietro
authors.forename: Ingrid
authors.initials: I
authors.lastname: Glurich
authors.forename: Susan F
authors.initials: SF
authors.lastname: Mickel
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Waring
authors.forename: Catherine A
authors.initials: CA
authors.lastname: McCarty
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism; D001794:Blood Pressure; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis; D000072556:Cholesterol 24-Hydroxylase; D004777:Environment; D004843:Epistasis, Genetic; D005260:Female; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism; D010865:Pilot Projects; D012307:Risk Factors; D051127:Scavenger Receptors, Class E / Q000235:genetics / Q000378:metabolism; D012907:Smoking / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
chemical_list: D001057:Apolipoproteins E; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; C495137:OLR1 protein, human; D051127:Scavenger Receptors, Class E; D014280:Triglycerides; D002097:C-Reactive Protein; D013250:Steroid Hydroxylases; D000072556:Cholesterol 24-Hydroxylase; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A