Genetic Evidence for the Involvement of Variants at APOE, BIN1, CR1, and PICALM Loci in Risk of Late-Onset Alzheimer's Disease and Evaluation for Interactions with APOE Genotypes

摘要

Alzheimer's disease (AD) is the most common form of dementia in older population. Growing evidence of genetic background that predisposes individuals to AD has been reported as the risk factors in recent years. The Department of Medical Genetics and the Immunology Research Centre investigated the distribution of 11 polymorphisms in 160 patients with late onset AD (LOAD) and in 163 healthy controls, using the sequencing technique. All participants were of Turkish Azeri ethnicity. We compared allele and genotype frequencies between the LOAD patients and control subjects using a chi-square or Fisher's exact test. Alleles and genotypes of APOE, PICALM rs3851179 and rs541458, and the BIN1 gene rs744373 polymorphism were significantly different between LOAD and control groups. The frequencies of the other investigated alleles were similar in the two groups. We also analyzed the association of BIN1, CR1 and PICALM SNPs with LOAD in subgroups stratified by the presence or absence of the APOE epsilon 4 allele. After adjusting for APOE, statistical analysis revealed that the association with PICALM rs541458 and BIN1 rs744373 were only significant among subjects without the APOE epsilon 4 allele.