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

Autor:	Bai H; Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, Ohio, USA.; Systems Biology and Bioinformatics, Department of Nutrition, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA., Naj AC; Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA., Benchek P; Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, Ohio, USA.; Department of Population & Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA., Dumitrescu L; Vanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Hohman T; Vanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Hamilton-Nelson K; John P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida, USA., Kallianpur AR; Genomic Medicine Institute, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, USA.; Department of Molecular Medicine, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA., Griswold AJ; John P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida, USA., Vardarajan B; Department of Neurology, The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA., Martin ER; John P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida, USA., Beecham GW; John P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida, USA., Below JE; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Schellenberg G; Penn Neurodegeneration Genomics Center, Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA., Mayeux R; Department of Neurology, The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA., Farrer L; Departments of Medicine (Biomedical Genetics), Neurology, Ophthalmology, Biostatistics, and Epidemiology, Boston University Schools of Medicine and Public Health, Boston, Massachusetts, USA., Pericak-Vance MA; John P. Hussman Institute for Human Genomics, University of Miami, Miami, Florida, USA., Haines JL; Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, Ohio, USA.; Department of Population & Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA., Bush WS; Cleveland Institute for Computational Biology, Case Western Reserve University, Cleveland, Ohio, USA.; Department of Population & Quantitative Health Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA.
Jazyk:	angličtina
Zdroj:	Alzheimer's & dementia : the journal of the Alzheimer's Association [Alzheimers Dement] 2023 Nov; Vol. 19 (11), pp. 4886-4895. Date of Electronic Publication: 2023 Apr 12.
DOI:	10.1002/alz.13050
Abstrakt:	Background: Haptoglobin (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. Methods: HP 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. Results: The 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. Discussion: The 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. (© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)
Databáze:	MEDLINE
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