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P2‐095: SORL1 is Genetically Associated with Alzheimer's Disease in Han Chinese
Author(s) -
Fuh Jong-Ling,
Liao Yi-Chu,
Lee Wei-Ju,
Wang Yen-Feng,
Chen Shih-Pin,
Wang Shuu-Jiun
Publication year - 2016
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2016.06.1300
Subject(s) - haplotype , single nucleotide polymorphism , apolipoprotein e , genetics , alzheimer's disease , odds ratio , biology , allele , linkage disequilibrium , medicine , genotype , disease , gene
Background:The recycling of the amyloid precursor protein via the endocytic pathway plays an important role in regulating the generation of amyloid b. The neuronal sortilin-related receptor gene (SORL1) was recently found to be associated with late-onset Alzheimer disease (AD) in several populations. The present study aims at testing its genetic effect in the Han Chinese population in Taiwan. Methods:A total of 798 AD cases, 157 patients with mild cognitive impairment (MCI) and 401 cognitive-intact elder controls were enrolled. Eight single nucleotide polymorphisms (SNPs) of SORL1 and apolipoprotein E (APOE) e2/e3/e4 alleles were genotyped. Global cognitive performance was assessed by mini-mental state examination in all participants, while comprehensive evaluation of each cognitive domain was performed in AD and MCI patients. Haploview software was used for haplotype analysis. Results: SORL1 rs1784933 was significantly associated with AD risk and the GG genotype carried a reduced risk for AD (odds ratio (OR) 1⁄4 0.78, p 1⁄4 0.008). After adjustment for age, sex, and APOE e4 allele, rs1784933 remained to be independent predictors of AD (Adj p 1⁄4 0.004). The influence of SORL1 rs1784933 was also evident in MCI patients (OR 1⁄4 0.69, p 1⁄4 0.012), and remained to be significant after adjustment of other covariates (Adj p 1⁄4 0.013). Intriguingly, the non-synonymous SNP rs2298813 leading to amino acid substitution from Threonine to Alanine at the vacuolar protein sorting domain was significantly associated with MCI susceptibility (OR 1⁄4 0.49, p 1⁄4 0.003). Haplotype analysis did not yield more significant results. Besides, none of the cognitive tests was related to SORL1 rs1784933 genotypes. Conclusions:The present study suggested that SORL1 polymorphism could alter the risk for AD and MCI in the Han Chinese population.