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Cited by 59Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsGenetic Associations and Epidemiology

A Common DIO2 Polymorphism and Alzheimer Disease Dementia in African and European Americans

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McAninch, Elizabeth A, Rajan, Kumar B, Evans, Denis A, Jo, Sungro, Chaker, Layal, Peeters, Robin P, Bennett, David A, Mash, Deborah C +1 more·2018·The Journal of Clinical Endocrinology & Metabolism
DOI 10.1210/jc.2017-01196PMC PMC6276710
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Abstract

Context: A common single nucleotide polymorphism in DIO2, Thr92AlaD2, has been associated with a transcriptome typically found in neurodegenerative diseases in postmortem human brain tissue. Objective: To determine whether Thr92AlaD2 is associated with incident Alzheimer disease (AD). Design: Population-based study; human brain tissue microarray. Setting: Community-based cohorts from Chicago and northeastern Illinois and religious clergymen from across the United States constituted the primary population. A representative sample of the U.S. population was used for secondary analyses. Participants: 3054 African Americans (AAs) and 9304 European Americans (EAs). Main Outcome Measure: Incident AD. Results: In the primary population, AAs with Thr92AlaD2 had 1.3 times [95% confidence interval (CI), 1.02 to 1.68; P = 0.048] greater odds of developing AD. AAs from a second population with Thr92AlaD2 showed a trend toward increased odds of dementia (odds ratio, 1.33; 95% CI, 0.99 to 1.78; P = 0.06) and 1.35 times greater odds of developing cognitive impairment not demented (CIND; 95% CI, 1.09 to 1.67; P = 0.006). Meta-analysis showed that AAs with Thr92AlaD2 had 1.3 times increased odds of developing AD/dementia (95% CI, 1.07 to 1.58; P = 0.008). In EAs, no association was found between Thr92AlaD2 and AD, dementia, or CIND. Microarray of AA brain tissue identified transcriptional patterns linked to AD pathogenesis. Conclusions: Thr92AlaD2 was associated with molecular markers known to underlie AD pathogenesis in AAs, translating to an observed phenotype of increased odds of developing AD/dementia in AAs in these populations. Thr92AlaD2 might represent one factor contributing to racial discrepancies in incident AD.

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  • Many patients complained of difficulties managing body weight and exhibited elevated serum cholesterol levels despite higher statin utilization.

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Authors
McAninch, E. A., Rajan, K. B., Evans, D. A., Jo, S., Chaker, L., Peeters, R. P., Bennett, D. A., Mash, D. C., & Bianco, A. C.
Affiliations
  • Rush University Medical Center (US)
  • Erasmus MC (NL)
  • University of Miami (US)
Corresponding author
Bianco, Antonio C
ORCID
Venue
The Journal of Clinical Endocrinology & Metabolism
Publisher
The Endocrine Society
Published
2018-02-22
Volume
103
Issue
5
Pages
1818-1826
ISSN
  • 0021-972X (ISSN-L)
  • 1945-7197
DOI
10.1210/jc.2017-01196
PMC
PMC6276710
OpenAlex
W2789887292
Cited by
59
References
39
Citations by year
2026: 2 · 2025: 3 · 2024: 1 · 2023: 9 · 2022: 6 · 2021: 9 · 2020: 11 · 2019: 13 · 2018: 5
FWCI
1.44
Type
journal article
Language
en
Open access
Locations
  • The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
Funders
  • National Institute on Aging (R01AG017917, P30AG010129, R01AG030146, RF1AG057532, R01AG051635, RC2AG036495, R01AG015819, P30AG010161, RC4AG039029, RF1AG015819, U01AG009740)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK065055)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords
DIO2, Alzheimer's disease, dementia, African Americans, European Americans, racial disparities, cognitive impairment, brain transcriptome, gene expression
MeSH terms
Iodothyronine Deiodinase Type II, Aged, Aged, 80 and over, Alanine, Alzheimer Disease, Black or African American, Dementia, Female, Gene Frequency, Humans, Iodide Peroxidase, Male, Middle Aged, Threonine, United States, Case-Control Studies, Amino Acid Substitution, Polymorphism, Single Nucleotide, White People

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