Association of post-transcriptional regulatory gene single nucleotide polymorphisms with Alzheimer's disease

BackgroundAlzheimer's disease (AD) is a progressive neurodegenerative characterized by amyloid-β (Aβ) peptide aggregation and tangles. Protein translation deregulation and viral exposures, including SARS-CoV-2, have been implicated in increased AD risk. Genes such as YIF1A, PABPC4, and MRPS27, which are involved in mRNA translation and protein folding have been linked to neurodegeneration and host responses to SARS-CoV-2.ObjectiveThis study investigates the association of three genetic variants, rs7945723G>A, rs6587A>G, and rs6831A>G, respectively correlated with YIF1A, PABPC4, and MRPS27, with AD, and explored their expression in COVID-19 samples to assess potential shared pathways.MethodsA KASP genotyping assay was performed on 127 AD patients and 250 controls. A Binary logistic regression model assessed the association between AD and the single nucleotide polymorphisms, adjusting for age, sex, body mass index, and education. Gene expression was quantified by RT-qPCR in nasopharyngeal samples from 32 COVID-19 patients and 39 controls. The Mann- Whitney test compared gene expression between groups, and logistic regression evaluated associations with COVID-19 status.ResultsResults showed that rs6587A>G in PABPC4 is significantly associated with AD risk with the GG genotype conferring increased susceptibility (OR = 4.3, p = 0.010). Gene expression analysis revealed no significant differences in PABPC4, YIF1A, or MRPS27 between COVID-19 and control groups.ConclusionsOur findings suggest that post-transcriptional regulatory mechanisms, particularly involving PABPC4, may contribute to AD-related pathways. Larger multi-ethnic cohorts and functional studies are needed to clarify the role of PABPC4 and potential shared mechanisms between AD and COVID-19.