The effects of the TOMM40 poly-T alleles on Alzheimer's disease phenotypes.

Abstract	The TOMM40 poly-T is a polymorphism in intron 6 of the TOMM40 gene, which is adjacent to and in linkage disequilibrium with APOE. Roses et al. identified the association between the length of TOMM40 poly-T with the risk and age of onset of late-onset Alzheimer's disease (LOAD). Following the original discovery, additional studies found associations between the TOMM40 poly-T and LOAD-related phenotypes independent of APOE genotypes, while others did not replicate these associations. Furthermore, the identity of the TOMM40 poly-T risk allele has been controversial between different LOAD-related phenotypes. Here, we propose a framework to address the conflicting findings with respect to the TOMM40 poly-T allele associations with LOAD phenotypes and their functional effects. The framework is used to interpret previous studies as means to gain insights regarding the nature of the risk allele, very long versus short. We suggest that the identity of the TOMM40 poly-T risk allele depends on the phenotype being evaluated, the ages of the study subjects at the time of assessment, and the context of the APOE genotypes. In concluding remarks, we outline future studies that will inform the mechanistic interpretation of the genetic data.
Authors	Ornit Chiba-Falek, William K Gottschalk, Michael W Lutz
Journal	Alzheimer's & dementia : the journal of the Alzheimer's Association (Alzheimers Dement) Vol. 14 Issue 5 Pg. 692-698 (05 2018) ISSN: 1552-5279 [Electronic] United States
PMID	29524426 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Review)
Copyright	Copyright © 2018 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
Chemical References	Apolipoproteins E Membrane Transport Proteins Mitochondrial Precursor Protein Import Complex Proteins TOMM40 protein, human Poly T
Topics	Age of Onset Alleles Alzheimer Disease (genetics) Apolipoproteins E (genetics) Genetic Predisposition to Disease Genotype Humans Membrane Transport Proteins (genetics) Mitochondrial Precursor Protein Import Complex Proteins Phenotype Poly T (genetics) Polymorphism, Single Nucleotide

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