SORL1 genetic variants modulate risk of amnestic mild cognitive impairment in northern Han Chinese.

The neuronal sortilin-related receptor (SORL1) has been reported to modulate the risk of Alzheimer's disease (AD) in a variety of populations, but replication studies have been inconsistent. Amnestic mild cognitive impairment (aMCI) is characterized by episodic memory impairment and represents the prodromal stage of AD. However, the relationship between SORL1 and aMCI remains unclear. This study aimed to investigate the relationship between SORL1 genetic variation and aMCI in the Han Chinese population. We conducted a case-control study using a single-nucleotide polymorphism (SNP), rs668387 (SNP8), in the 5' region of SORL1, and three SNPs [rs2070045 (SNP19), rs3824968 (SNP23), rs2282649 (SNP24)] in the 3' region of SORL1, along with a haplotype analysis, in 139 aMCI patients and 213 cognitively-healthy controls from a northern Han Chinese population. We observed that SNP19 had a significantly different allele frequency between aMCI patients and controls (p = 0.006). Moreover, the GAT haplotype at SNPs 19-23-24 was associated with an increased risk of aMCI [odds ratio (OR) 1.377], while the TTC haplotype at SNPs 19-23-24 was associated with a decreased risk (OR 0.708). These results indicated that the SNPs in the 3' region of SORL1 are associated with aMCI in northern Han Chinese.