The SORL1 polymorphism rs985421 may confer the risk for amnestic mild cognitive impairment and Alzheimer's disease in the Han Chinese population

• The ‘A’ allele of rs985421 in the SORL1 gene may increase the risk for SAD and aMCI in the Han Chinese population.
• The ‘A’ allele of rs985421 might be an ApoE ɛ4-independent risk factor for SAD.
• Future research should be performed to find other possible causative variants.

Although the pathogenetic mechanisms driving Alzheimer's disease (AD) are unclear, genetic variations may play an important role. Previous studies have identified that single nucleotide polymorphisms (SNPs) in the sortilin-related receptor, L (DLR class) A repeats containing (SORL1) gene are associated with AD or amnestic mild cognitive impairment (aMCI) patients. However, the association of SORL1 variants with AD or aMCI susceptibility in the Han Chinese population has not been adequately reported. Thus, we conducted a case-control study in 106 sporadic AD patients, 67 aMCI patients, and 179 healthy control Han Chinese subjects to determine whether SORL1 genetic variations alter the risk for AD or aMCI. Using the LDR–PCR method to genotype five polymorphisms in SORL1, we found significant associations (for AD: OR = 1.968, 95% CI = 1.273–3.042; for aMCI: OR = 2.210, 95% CI = 1.353–3.610) between the ‘A’ allele of the SORL1 SNP rs985421 and AD and aMCI, which may represent an ApoE ɛ4-independent risk factor for SAD. These findings suggest that the SORL1 SNP rs985421 may alter the risk for sporadic AD and aMCI in the Han Chinese population.