SORL1 Polymorphisms in Mexican Patients with Alzheimer's Disease.

The present study evaluated the risk effect of 12 Single Nucleotide Polymorphisms in the SORL1 gene in the Mexican population using Late-Onset Alzheimer's Disease (LOAD) and control subjects. Considering APOE as the strongest genetic risk factor for LOAD, we conducted interaction analyses between single nucleotide polymorphisms (SNPs) and the APOE genotype. METHODS: Patients were interviewed during their scheduled visits at neurologic and geriatric clinics from different institutions. The LOAD diagnosis included neurological, geriatric, and psychiatric examinations, as well as the medical history and neuroimaging. Polymorphisms in SORL1 were genotyped by real-time PCR in 156 subjects with LOAD and 221 controls. APOE genotype was determined in each study subject. Allelic, genotypic, and haplotypic frequencies were analyzed; an ancestry analysis was also performed. RESULTS: The A/A genotype in rs1784933 might be associated with an increased LOAD risk. Two blocks with high degree linkage disequilibrium (LD) were identified. The first block composed by the genetic variants rs668387, rs689021 and rs641120 showed a positive interaction (mainly the rs689021) with rs1784933 polymorphism. Moreover, we found a significant association between the APOE ε4 allele carriers and the variant rs2070045 located in the second LD block. CONCLUSION: The rs1784933 polymorphism is associated with LOAD in Mexican patients. In addition, the presence of APOE ε4 allele and SORL1 variants could represent a genetic interaction effect that favors LOAD risk in the Mexican population. SNPs have been proposed as genetic markers associated with the development of LOAD that can support the clinical diagnosis. Future molecular studies could help understand sporadic Alzheimer's Disease (AD) among the Mexican population, where currently there is a sub-estimate number in terms of disease frequency and incidence.

Evaluation of inflammation-related genes polymorphisms in Mexican with Alzheimer's disease: a pilot study.

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.