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.
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: Patrick G Kehoe; Hagit Katzov; Lars Feuk; Anna M Bennet; Boo Johansson; Björn Wiman; Ulf de Faire; Nigel J Cairns; Gordon K Wilcock; Anthony J Brookes; Kaj Blennow; Jonathan A Prince Journal: Hum Mol Genet Date: 2003-04-15 Impact factor: 6.150
Authors: Heike Kölsch; D Lütjohann; M Ludwig; A Schulte; U Ptok; F Jessen; K von Bergmann; M L Rao; W Maier; R Heun Journal: Mol Psychiatry Date: 2002 Impact factor: 15.992
Authors: Joan Lindsay; Danielle Laurin; René Verreault; Réjean Hébert; Barbara Helliwell; Gerry B Hill; Ian McDowell Journal: Am J Epidemiol Date: 2002-09-01 Impact factor: 4.897
Authors: L A Farrer; L A Cupples; J L Haines; B Hyman; W A Kukull; R Mayeux; R H Myers; M A Pericak-Vance; N Risch; C M van Duijn Journal: JAMA Date: 1997 Oct 22-29 Impact factor: 56.272
Authors: Olivia Belbin; Kristelle Brown; Hui Shi; Christopher Medway; Richard Abraham; Peter Passmore; David Mann; A David Smith; Clive Holmes; Bernadette McGuinness; David Craig; Donald Warden; Reinhard Heun; Heike Kölsch; Seth Love; Noor Kalsheker; Julie Williams; Michael J Owen; Minerva Carrasquillo; Steven Younkin; Kevin Morgan; Patrick G Kehoe Journal: J Alzheimers Dis Date: 2011 Impact factor: 4.472
Authors: Andrew McDavid; Paul K Crane; Katherine M Newton; David R Crosslin; Wayne McCormick; Noah Weston; Kelly Ehrlich; Eugene Hart; Robert Harrison; Walter A Kukull; Carla Rottscheit; Peggy Peissig; Elisha Stefanski; Catherine A McCarty; Rebecca Lynn Zuvich; Marylyn D Ritchie; Jonathan L Haines; Joshua C Denny; Gerard D Schellenberg; Mariza de Andrade; Iftikhar Kullo; Rongling Li; Daniel Mirel; Andrew Crenshaw; James D Bowen; Ge Li; Debby Tsuang; Susan McCurry; Linda Teri; Eric B Larson; Gail P Jarvik; Chris S Carlson Journal: PLoS One Date: 2013-06-10 Impact factor: 3.240