SORL1 Polymorphisms in Mexican Patients with Alzheimer's Disease

Area of Science:

• Genetics
• Neuroscience
• Population Health

Background:

• Late-Onset Alzheimer's Disease (LOAD) is a complex neurodegenerative disorder with significant genetic components.
• The Apolipoprotein E (APOE) gene is a major genetic risk factor for LOAD.
• The Sortilin Related Receptor 1 (SORL1) gene has been implicated in Alzheimer's Disease (AD) pathogenesis.

Purpose of the Study:

• To evaluate the risk effect of 12 Single Nucleotide Polymorphisms (SNPs) in the SORL1 gene in the Mexican population.
• To investigate potential interactions between SORL1 SNPs and the APOE genotype in LOAD risk.
• To identify genetic markers for LOAD in the Mexican population.

Main Methods:

• Case-control study including 156 LOAD patients and 221 controls from the Mexican population.
• Genotyping of SORL1 polymorphisms using real-time PCR.
• APOE genotyping and analysis of allelic, genotypic, and haplotypic frequencies.
• Linkage Disequilibrium (LD) and interaction analyses between SNPs and APOE genotype.

Main Results:

• The A/A genotype in rs1784933 (SORL1) was associated with an increased risk of LOAD.
• Two blocks of high LD were identified within SORL1 variants.
• A significant interaction was observed between rs1784933 and other SORL1 variants (rs668387, rs689021, rs641120).
• A significant association was found between APOE ε4 allele carriers and the SORL1 variant rs2070045.

Conclusions:

• The rs1784933 polymorphism in SORL1 is associated with LOAD in Mexican patients.
• Interactions between APOE ε4 and SORL1 variants may contribute to increased LOAD risk in this population.
• SNPs in SORL1 may serve as potential genetic markers for LOAD, aiding clinical diagnosis and future research into sporadic AD in Mexico.