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Several studies have evaluated the role of polymorphisms in the promoter region of APOE gene that encodes apolipoprotein E (APOE) and the susceptibility to Alzheimer's disease (AD). The aim of this literature review and meta-analysis was to investigate the relationship between the APOE promoter region single nucleotide polymorphisms (SNPs) (rs449647, -491A/T; rs769446, -427T/C and rs405509 -219T/G) and the risk of developing AD. Eligible controlled studies published up to November 2016 were retrieved from main online scientific and medical databases. Odds ratio (OR) and 95 % confidence interval (CI) were used to calculate the strength of the relationship. A total of 23 publications (19 for rs449647, ten for rs769446 and ten for rs405509) were retrieved that included 5,703 patients with AD and 5,692 controls. The C allele of the rs769446 variant of the promoter region of APOE gene was significantly associated with an increase of risk of AD (OR = 1.271, 95 % CI = 1.114-1.449, P < 0.0001), while other genetic models of this variant were not related with susceptibility to AD. Rs449647 and rs405509 polymorphisms of APOE gene were not associated with an increase of risk of AD. The findings of this literature review and meta-analysis have shown that rs769446 polymorphism in the promoter region of APOE gene could be a risk factor for AD. Future large-scale studies on the role of polymorphisms in the promoter region of APOE gene in AD are still awaited.
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