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Regulatory region single nucleotide polymorphisms of the apolipoprotein E gene as risk factors for Alzheimer's disease.
Neuroscience Letters 2018 September 26
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by a complex aetiology. The ε4 allel of the apolipoprotein E gene (APOE) is the only confirmed genetic risk factor for the development of AD. In addition, polymorphisms at the promoter region of the APOE gene are assumed to modulate the susceptibility to AD by their different affinity to the transcription factors thus affecting the expression of the gene. In the presented study, we investigated the association between -491 A/T (rs449647), -427C/T, (rs769446) and -219 T/G (rs405509) single nucleotide polymorphisms (SNPs) of APOE gene and AD risk in the Polish population. We found that only the -491 T allele and -491 A/T genotype acted as protective factors against AD, whereas the -219 T/G heterozygosity increased risk for AD in APOE ε4 carriers but not in APOE ε4 non-carriers. What is more, haplotype frequency estimation showed significant positive for A-T-T-C-C and A-T-G-C-C haplotypes or negative for A-T-T-T-C and T-T-T-T-C haplotypes associations with AD. These results contribute to the evidence that APOE promoter polymorphisms modulate risk for AD.
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