title: SORCS1 and APOE polymorphisms interact to confer risk for late-onset Alzheimer's disease in a Northern Han Chinese population.
abstract: 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.
authors.affiliation: Department of Neurology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao 266071, China.
authors.forename: Hui-Fu
authors.initials: HF
authors.lastname: Wang
authors.forename: Jin-Tai
authors.initials: JT
authors.lastname: Yu
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Qiu-Yan
authors.initials: QY
authors.lastname: Liu
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Ma
authors.forename: Hua-Min
authors.initials: HM
authors.lastname: Ding
authors.forename: Lan
authors.initials: L
authors.lastname: Tan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000544:Alzheimer Disease / Q000453:epidemiology* / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D044466:Asian People; D002681:China / Q000453:epidemiology; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D016015:Logistic Models; D008297:Male; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics*; D012306:Risk
chemical_list: D001057:Apolipoproteins E; D011956:Receptors, Cell Surface; C472780:SORCS1 protein, human