The rs1277306 Variant of the REST Gene Confers Susceptibility to Cognitive Aging in an Elderly Taiwanese Population.

BACKGROUND/AIMS: There is growing evidence that the RE1-silencing transcription factor (REST) gene may contribute to cognitive aging and Alzheimer diseases. In this replication study, we reassessed whether single nucleotide polymorphisms (SNPs) within the REST gene are linked with cognitive aging independently and/or through complex interactions in an older Taiwanese population.

METHODS: A total of 634 Taiwanese subjects aged over 60 years from the Taiwan Biobank were analyzed. Mini-Mental State Examination (MMSE) scores were performed for all subjects to weigh cognitive functions.

RESULTS: Our data showed that the REST rs1277306 SNP was significantly associated with cognitive aging among all subjects (p = 0.0052). Furthermore, the association remained significant for individuals without APOE ε4 allele (p = 0.0092), but not for individuals with at least 1 APOE ε4 allele. This association remained significant after Bonferroni correction. Additionally, we found the interactions between the rs1713985 and rs1277306 SNPs on cognitive aging (p = 0.016). However, the 3-marker haplotype derived from the rs1713985, rs3796529, and rs7680734 SNPs in the REST gene demonstrated no association with cognitive aging.

CONCLUSION: Our study indicates that the REST gene may contribute to susceptibility to cognitive aging independently as well as through SNP-SNP and APOE-REST interactions.