A single nucleotide polymorphism in DIO2, Thr92AlaD2, has been associated with a transcriptome typically found in neurodegenerative diseases in postmortem human brain tissue.
To determine whether Thr92AlaD2 is associated with incident Alzheimer’s disease (AD).
Population-based study; human brain tissue microarray.
Community-based cohorts from Chicago, Illinois and northeastern Illinois, as well as religious clergymen from across the U.S. made up the primary population. A representative sample of the U.S. population was used for secondary analyses.
3054 African (AA) and 9304 European Americans (EA).
Incident AD.
In the primary population, AAs with Thr92AlaD2 had 1.3 times (95% CI, 1.02 to 1.68; P=0.048) higher odds of developing AD. AAs from a second population with Thr92AlaD2 had a trend towards increased odds of dementia (odds ratio (OR) 1.33; 95% CI, 0.99 to 1.78; P=0.06); they also exhibited 1.35 times higher 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 there was no association between Thr92AlaD2 and AD, dementia, or CIND. Microarray of AA brain tissue identified transcriptional patterns linked to AD pathogenesis.
Thr92AlaD2 is associated with molecular markers known to underlie AD pathogenesis in AAs; this translates to an observed phenotype of increased odds of developing AD/dementia in AAs in these populations. Thr92AlaD2 may represent one factor contributing to racial discrepancies in incident AD.

A Common DIO2 Polymorphism And Alzheimer’s Disease Dementia in African And European Americans.

McAninch EA, Rajan KB, Evans DA, Jo S, Chaker L, Peeters RP, Bennett DA, Mash DC, Bianco AC. J Clin Endocrinol Metab. 2018 PMID: 29481662

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