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

作者：McAninch Elizabeth A; Rajan Kumar B; Evans Denis A; Jo Sungro; Chaker Layal; Peeters Robin P; Bennett David A; Mash Deborah C; Bianco Antonio C^*

来源：Journal of Clinical Endocrinology & Metabolism, 2018, 103(5): 1818-1826.

DOI：10.1210/jc.2017-01196

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.

• 出版日期2018-5