Apolipoprotein E Gene Revisited: Contribution of Rare Variants to Alzheimer’s Disease Susceptibility in Southern Chinese

Author(s): Anita Yee, Nancy B.Y. Tsui, Rick Y.C. Kwan, Angela Y.M. Leung, Claudia K.Y. Lai, Teresa Chung, Johnson Y.N. Lau, Manson Fok, David L.K. Dai*, Lok-Ting Lau*

Journal Name: Current Alzheimer Research

Volume 18 , Issue 1 , 2021

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Background: APOE ε4 is the best-known risk factor for late-onset alzheimer’s disease (AD). Population studies have demonstrated a relatively low prevalence of APOE ε4 among Chinese population, implying additional risk factors that are Chinese-specific may exist. Apart from - alleles, genetic variation profile along the full-length APOE has rarely been investigated.

Objective: In this study, we filled this gap by comprehensively determining all genetic variations in APOE and investigated their potential associations with late-onset AD and mild cognitive impairment (MCI) in southern Chinese.

Methods: Two hundred and fifty-seven southern Chinese participants were recruited, of whom 69 were AD patients, 83 had MCI, and 105 were normal controls. Full-length APOE from promoter to 3′UTR regions were sequenced. Genetic variants were identified and compared among the three groups.

Results: While APOE ε4 was more significantly found in AD patients, the prevalence of APOE ε4 in southern Chinese AD patients was the lowest when compared to other areas of China and nearby regions, as well as other countries worldwide. We further identified 13 rare non-singleton variants in APOE. Significantly more AD patients carried any of the rare non-singleton variants than MCI and normal subjects. Such difference was observed in the non-carriers of ε4-allele only. Among the identified rare variants, the potential functional impact was predicted for rs532314089, rs553874843, rs533904656 and rs370594287.

Conclusion: Our study suggests an ethnic difference in genetic risk composition of AD in southern Chinese. Rare variants on APOE are a potential candidate for AD risk stratification biomarker in addition to APOE-ε4.

Keywords: Alzheimer's disease, mild cognitive impairment, Chinese, APOE, rare variants, genetics.

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Year: 2021
Published on: 24 March, 2021
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DOI: 10.2174/1567205018666210324111401
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