Apolipoprotein gene E4 allele promoter polymorphisms as risk factors for Alzheimer's disease

Alzheimer's disease is a complex neurodegenerative disorder, characterized by progressive cognitive decline and distinct neuropathology. The apolipoprotein gene E4 allele (APOE 4) is a major risk factor for the disease. Promoter polymorphisms at - 491 and - 427 may also contribute to the risk. We examined the two polymorphisms in 178 Alzheimer's patients and 141 controls. The - 491 AA genotype was overrepresented among the patients (68 versus 54%, P=0.01). However, in patients who were APOE4 carriers, the - 491 AA genotype more than doubled the risk [odds ratio (OR)=2.5; 95% confidence interval (Cl) = 1.2-5.4], especially in combination with - 427TT [odds ratio (OR)=3.3; 95% confidence interval (Cl)=1.5-77]. Moreover, the -491A/-427T/APOE4/APOC1A haplotype was threefold higher for patients. These results contribute to the evidence that regulation of APOE4 expression modulates risk for Alzheimer's disease. Psychiatr Genet 15:271-275 (c) 2005 Lippincott Williams & Wilkins.