Abstract
Amyloid peptide is able to promote the activation of microglia and astrocytes in Alzheimer’s disease (AD), and this stimulates the production of pro-inflammatory cytokines. Inflammation contributes to the process of neurodegeneration and therefore is a key factor in the development of AD. Some of the most important proteins involved in AD inflammation are: clusterin (CLU), complement receptor 1 (CR1), C reactive protein (CRP), tumor necrosis factor α (TNF-α), the interleukins 1α (IL-1α), 6 (IL-6), 10 (IL-10) and cyclooxygenase 2 (COX-2). In particular, COX-2 is encoded by the prostaglandin-endoperoxide synthase 2 gene (PTGS2). Since variations in the genes that encode these proteins may modify gene expression or function, it is important to investigate whether these variations may change the developing AD. The aim of this study was to determine whether the presence of polymorphisms in the genes encoding the aforementioned proteins is associated in Mexican patients with AD. Fourteen polymorphisms were genotyped in 96 subjects with AD and 100 controls; the differences in allele, genotype and haplotype frequencies were analyzed. Additionally, an ancestry analysis was conducted to exclude differences in genetic ancestry among groups as a confounding factor in the study. Significant differences in frequencies between AD and controls were found for the single-nucleotide polymorphism (SNP) rs20417 within the PTGS2 gene. Ancestry analysis revealed no significant differences in the ancestry of the compared groups, and the association was significant even after adjustment for ancestry and correction for multiple testing, which strengthens the validity of the results. We conclude that this polymorphism plays an important role in the development of the AD pathology and further studies are required, including their proteins.
Highlights
Alzheimer’s disease (AD) is a neurodegenerative disease which major symptom is the impairment of memory and other cognitive functions (Collette et al, 1999; Di Paola et al, 2007)
Considering all of the above mentioned, the aim of this study was to evaluate a set of candidate polymorphisms in inflammation-related genes, and to determine whether they are associated with the risk of developing AD in the Mexican population, considering the genetic ancestry of the study subjects
It is important to mention that this is the first study in Mexican population that considers the analysis of ancestry in AD patients in which it was possible to find that the presence of the GG genotype in the single-nucleotide polymorphism (SNP) rs20417 displayed an association with AD patients in our population
Summary
Alzheimer’s disease (AD) is a neurodegenerative disease which major symptom is the impairment of memory and other cognitive functions (Collette et al, 1999; Di Paola et al, 2007). It has been estimated that the global prevalence of dementia is around 4.5% and that AD accounts for 65% of the total number of dementia Alzheimer’s type (DAT; Kalaria et al, 2008; Rizzi et al, 2014), which places AD as the major global cause of dementia. The definitive diagnose of AD can be only performed by post mortem histological analysis, in which certain distinctive lesions must be found. These lesions consist of protein aggregates known as neuritic plaques (NPs), composed of the amyloid-β peptide (Wong et al, 1985), and neurofibrillary tangles (NFTs), composed of hyperphosphorylated tau protein (Kosik et al, 1986)
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