Effect of APOE genotype and promoter polymorphism on risk of Alzheimer's disease

Objective: To verify the association between APOE gene promoter polymorphis ms and the development of AD and to determine whether the effect of promote r polymorphisms on AD is independent of the APOE epsilon4 allele, Backgroun d: Three polymorphisms in the APOE promoter have been shown to modify APOE expression in vitro. Several studies have suggested that these polymorphism s may also modulate risk for AD, either independently or by modifying the e ffect of the APOE coding polymorphism. Methods: The authors analyzed allele and genotype distributions for APOE and all three known APOE promoter poly morphisms (-491 A/T, -427 T/C, and -219 G/T) in a study group consisting of 237 subjects with AD and 274 age-matched controls, They then used log-line ar and logistic regression analyses to test for possible interactions betwe en APOE genotype and the promoter polymorphisms on risk of AD. Conclusion: A strong association between the APOE epsilon4 allele and AD was detected r egardless of promoter polymorphism status. In addition, the -491 AA genotyp e appears to be an independent genetic risk factor for AD, The -427 T/C pol ymorphism and the -219 T/G polymorphism were not directly associated with A D.