Amyloid-β-related genes SORL1 and ACE are genetically associated with risk for late-onset Alzheimer disease in the Chinese population.
Late-onset Alzheimer Disease (LOAD) is a common neurodegenerative disease, and one of its major pathologic characteristics is senile plaques. Proteins encoded by SORL1 and ACE have been shown to be related to the processing, trafficking, and degradation of Amyloid-β, the principal component of senile plaques. In this paper, we investigated whether SORL1 and ACE are associated with LOAD. We recruited 144 LOAD patients and 476 controls from Shanghai, China and conducted a case-control study on 9 single-nucleotide polymorphisms (SNPs): 6 in SORL1 (rs2070045, rs661057, rs668387, rs689021, rs3824968, rs2282649) and 3 in ACE (rs1800764, rs4343, rs1799752). Despite the small case sample size (144), we observed that rs1800764, rs4343, rs1799752 in ACE, and rs2070045, rs3824968, rs2282649 in SORL1 showed significantly different allele frequencies between patients and controls (P=4.57×10, 5.24×10, 1.95×10, 1.77×10, 6.44×10, and 3.11×10, respectively). Moreover, haplotypes on ACE and on SORL1 were significantly associated with LOAD (all P-value<0.009 in ACE and all P-value <0.003 in SORL1). In ACE, we found the most significant protective haplotype encompasses SNPs rs2070045, rs3824968, and rs2282649 (C-G-D: OR=0.20, P=8.96×10). In SORL1, we detected a "complementary" haplotype (G-A-T: OR=1.54, P=2.67×10; T-T-C: OR=0.63, P=2.36×10) composed of SNPs rs2070045, rs3824968, and rs2282649. In addition, we carried out meta-analysis with 3 other Asian populations on 3 SNPs in SORL1 (rs2070045, rs3824968, and rs2282649). Results supported our initial finding that these 3 SNPs were associated with LOAD. Our data suggested that SORL1 and ACE might play a role in LOAD susceptibility among Han Chinese.
Ning
Mei
M
*Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences †Institutes of Biomedical Sciences, Fudan University ‡Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai 200030, China.
Yang
Yifeng
Y
Zhang
Zhou
Z
Chen
Zhuo
Z
Zhao
Teng
T
Zhang
Di
D
Zhou
Daizhan
D
Xu
Jie
J
Liu
Zhe
Z
Wang
Yabing
Y
Liu
Yun
Y
Zhao
Xinzhi
X
Li
Weidong
W
Li
Sheng
S
He
Lin
L
D017668:Age of Onset; D000368:Aged; D000544:Alzheimer Disease / Q000235:genetics*; D016229:Amyloid beta-Peptides / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D060005:Genotyping Techniques; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000235:genetics*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors
D016229:Amyloid beta-Peptides; D026502:LDL-Receptor Related Proteins; D026901:Membrane Transport Proteins; C102582:SORL1 protein, human; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A