Research ReportSORCS1 and APOE polymorphisms interact to confer risk for late-onset Alzheimer's disease in a Northern Han Chinese population

Sortilin-related VPS domain containing receptor 1 (SORCS1), is located on chromosome 10q23.3, a chromosomal region of interest in Alzheimer's disease (AD) defined by many genome-wide and chromosome10-specific studies. Recently, three intronic variants (rs12571141, rs17277986 and rs6584777) within SORCS1 were reported to be associated with AD in Caucasian. In order to assess the involvement of the SORCS1 polymorphisms in the progression of late-onset AD (LOAD), we conducted an independent replication study in 1198 unrelated Northern Han Chinese subjects comprising 598 LOAD patients and 600 healthy controls matched for gender and age. The results revealed no significant differences in the distributions of genotype or allele between LOAD and control groups in the total sample. However, when these data were stratified by the Apolipoprotein E (APOE) ε4 status, we observed significant differences in the genotypes and allele frequencies (rs12571141: P = 0.001, rs17277986: P = 0.005, rs6584777: P = 0.023) in APOE ε4 allele carriers. Moreover, the association was further demonstrated in logistic regression analysis (rs12571141: P = 0.002, OR = 0.424; rs17277986: P = 0.004, OR = 0.447; rs6584777: P = 0.019, OR = 0.523) and haplotype analysis (GCC: P = 0.002, ATT: P = 0.002, ACC: P = 0.025) in this subset. Our data suggested that SORCS1 was in interaction with APOE in the development of LOAD in a Northern Han Chinese population.

► SORCS1 SNPs (rs12571141, rs17277986 and rs6584777) interact with APOE to confer risk for LOAD. ► The minor alleles of the three associated variants are protective factors for LOAD. ► SORCS1 was in interaction with ApoE in the development of AD in Han Chinese.