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Amyloid-β-Related Genes SORL1 and ACE are Genetically Associated With Risk for Late-onset Alzheimer Disease in the Chinese Population

Ning, Mei PhD*; Yang, Yifeng PhD*; Zhang, Zhou PhD*; Chen, Zhuo PhD*; Zhao, Teng PhD*; Zhang, Di PhD*; Zhou, Daizhan PhD*; Xu, Jie PhD*; Liu, Zhe PhD*; Wang, Yabing PhD*; Liu, Yun PhD*,†; Zhao, Xinzhi PhD; Li, Weidong PhD; Li, Sheng PhD*; He, Lin PhD*,†,‡

Alzheimer Disease & Associated Disorders: October–December 2010 - Volume 24 - Issue 4 - p 390–396
doi: 10.1097/WAD.0b013e3181e6a575
Original Articles

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=4.57×10−2, 5.24×10−3, 1.95×10−4, 1.77×10−4, 6.44×10−3, and 3.11×10−3, 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=8.96×10−14). In SORL1, we detected a “complementary” haplotype (G-A-T: OR=1.54, P=2.67×10−3; T-T-C: OR=0.63, P=2.36×10−3) 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.

*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

Supported by grants (2006AA02A407, 2006CB910601, 2006BAI05A05, 2007CB947300 and 07DZ22917), the Shanghai Leading Academic Discipline Project (B205), the Shanghai Municipality Science & Technology Commission (05JC14090, 07DJ14005), the Chinese Nutrition Society (05015), the Knowledge Innovation Program of Shanghai Institutes for Biological Sciences, the Chinese Academy of Sciences (2007KIP210, 2009KIP305), and the Chinese Academy of Sciences (KSCX2-YW-R-01, KSCX2-YW-N-034).

Mei Ning, PhD and Yifeng Yang, PhD These researchers contributed equally to this work.

Reprints: Lin He, PhD and Sheng Li, PhD, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 294 Taiyuan Road, Shanghai 200031, PR China (e-mail: sli01@sibs.ac.cn or helin@bio-x.cn).

Received October 7, 2009

Accepted March 15, 2010

© 2010 Lippincott Williams & Wilkins, Inc.