TY - JOUR
T1 - A Common DIO2 Polymorphism and Alzheimer Disease Dementia in African and European Americans
AU - McAninch, Elizabeth A.
AU - Rajan, Kumar B.
AU - Evans, Denis A.
AU - Jo, Sungro
AU - Chaker, Layal
AU - Peeters, Robin P.
AU - Bennett, David A.
AU - Mash, Deborah C.
AU - Bianco, Antonio C.
N1 - Publisher Copyright:
Copyright © 2018 Endocrine Society.
PY - 2018/5/1
Y1 - 2018/5/1
N2 - 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.
AB - 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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U2 - 10.1210/jc.2017-01196
DO - 10.1210/jc.2017-01196
M3 - Article
C2 - 29481662
AN - SCOPUS:85047199083
SN - 0021-972X
VL - 103
SP - 1818
EP - 1826
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 5
ER -