A haptoglobin (HP) structural variant alters the effect of <i>APOE</i> alleles on Alzheimer's disease-Reference-Cited by-同舟云学术

A haptoglobin (HP) structural variant alters the effect of APOE alleles on Alzheimer's disease

Published:2023-04-12 Issue:11 Volume:19 Page:4886-4895
ISSN:1552-5260
Container-title:Alzheimer's & Dementia
language:en
Short-container-title:Alzheimer's & Dementia

Author:

Bai Haimeng¹²,Naj Adam C.³,Benchek Penelope¹⁴,Dumitrescu Logan⁵,Hohman Timothy⁵,Hamilton‐Nelson Kara⁶,Kallianpur Asha R.⁷⁸,Griswold Anthony J.⁶,Vardarajan Badri⁹,Martin Eden R.⁶,Beecham Gary W.⁶,Below Jennifer E.¹⁰,Schellenberg Gerard¹¹,Mayeux Richard⁹,Farrer Lindsay¹²,Pericak‐Vance Margaret A.⁶,Haines Jonathan L.¹⁴,Bush William S.¹⁴,

Affiliation:

1. Cleveland Institute for Computational Biology Case Western Reserve University Cleveland Ohio USA

2. Systems Biology and Bioinformatics Department of Nutrition Case Western Reserve University School of Medicine Cleveland Ohio USA

3. Department of Pathology and Laboratory Medicine University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA

4. Department of Population & Quantitative Health Sciences Case Western Reserve University School of Medicine Cleveland Ohio USA

5. Vanderbilt Memory & Alzheimer's Center Vanderbilt University Medical Center Nashville Tennessee USA

6. John P. Hussman Institute for Human Genomics University of Miami Miami Florida USA

7. Genomic Medicine Institute Lerner Research Institute Cleveland Clinic Foundation Cleveland Ohio USA

8. Department of Molecular Medicine Case Western Reserve University School of Medicine Cleveland Ohio USA

9. Department of Neurology The Taub Institute for Research on Alzheimer's Disease and the Aging Brain Columbia University New York New York USA

10. Vanderbilt Genetics Institute Vanderbilt University Medical Center Nashville Tennessee USA

11. Penn Neurodegeneration Genomics Center Department of Pathology and Laboratory Medicine University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA

12. Departments of Medicine (Biomedical Genetics) Neurology, Ophthalmology, Biostatistics, and Epidemiology Boston University Schools of Medicine and Public Health Boston Massachusetts USA

Abstract

AbstractBackgroundHaptoglobin (HP) is an antioxidant of apolipoprotein E (APOE), and previous reports have shown HP binds with APOE and amyloid beta (Aβ) to aid its clearance. A common structural variant of the HP gene distinguishes it into two alleles: HP1 and HP2.MethodsHP genotypes were imputed in 29 cohorts from the Alzheimer's Disease Genetics Consortium (N = 20,512). Associations between the HP polymorphism and Alzheimer's disease (AD) risk and age of onset through APOE interactions were investigated using regression models.ResultsThe HP polymorphism significantly impacts AD risk in European‐descent individuals (and in meta‐analysis with African‐descent individuals) by modifying both the protective effect of APOE ε2 and the detrimental effect of APOE ε4. The effect is particularly significant among APOE ε4 carriers.DiscussionThe effect modification of APOE by HP suggests adjustment and/or stratification by HP genotype is warranted when APOE risk is considered. Our findings also provided directions for further investigations on potential mechanisms behind this association.

Publisher

Wiley

Subject

Psychiatry and Mental health,Cellular and Molecular Neuroscience,Geriatrics and Gerontology,Neurology (clinical),Developmental Neuroscience,Health Policy,Epidemiology

Reference50 articles.

1. Gene Dose of Apolipoprotein E Type 4 Allele and the Risk of Alzheimer's Disease in Late Onset Families

2. Alzheimer's Disease: The Amyloid Cascade Hypothesis

3. Microtubule-associated protein tau (tau) is a major antigenic component of paired helical filaments in Alzheimer disease.

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