An inherited variable poly-T repeat genotype in TOMM40 in Alzheimer disease
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I coauthored a recently published research article describing a variable length, poly-T polymorphism in the TOMM40 gene, adjacent to apolipoprotein E (APOE) on chromosome 19, that accounts for the age at onset distribution for a complex disease, late-onset Alzheimer disease. These new data explain the mean age at disease onset for patients with the APOE4/4 genotype and differentiate 2 forms of TOMM40 poly-T polymorphisms linked to APOE, with each form associated with a different age at disease onset distribution. When linked to APOE3 (encoding the epsilon3 isoform of APOE), the longer TOMM40 poly-T repeats (19-39 nucleotides) at the rs10524523 (hereafter, 523) locus are associated with earlier age at onset and the shorter TOMM40 523 alleles (11-16 nucleotides) are associated with later age at onset. The data suggest that the poly-T alleles are codominant, with the age at onset phenotype determined by the 2 inherited 523 alleles, but with variable expressivity. Additional data will further refine the relationship between the length of the poly-T alleles and age at disease onset and determine if the relationship is linear.
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The TOMM40 gene, and by extension its protein product, could potentially impact LOAD.
“from a strict association perspective it does appear that the TOMM40 gene, and by extension its protein product, could potentially impact LOAD.”
From The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives (2014) · cites this paper as [143]
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- Authors
- Roses, A. D.
- Affiliations
- Duke University (US)
- Corresponding author
- Roses, Allen D.
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2010-05-01
- Volume
- 67
- Issue
- 5
- Pages
- 536-41
- ISSN
- 0003-9942 (ISSN-L)
- PMC
- PMC3140162
- OpenAlex
- W2135615076
- Cited by
- 118
- References
- 13
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 2 · 2023: 4 · 2022: 5 · 2021: 8 · 2020: 6 · 2019: 3 · 2018: 7 · 2017: 11 · 2016: 8 · 2015: 5 · 2014: 6 · 2013: 15 · 2012: 12
- FWCI
- 9.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Science Foundation Arizona
- National Institute on Aging (P30AG028377, AG019610, AG031581, AG028377, R01AG031581, P30AG019610, RC1AG035635)
- National Institute of Neurological Disorders and Stroke (R01NS059873)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- TOMM40, Alzheimer's disease, late-onset Alzheimer's disease, age of onset, apolipoprotein E, codominant inheritance, variable expressivity, chromosome 19, genetic susceptibility
- MeSH terms
- Mitochondrial Precursor Protein Import Complex Proteins, Alzheimer Disease, Apolipoproteins E, Chromosomes, Human, Pair 19, Gene Frequency, Humans, Polymorphism, Genetic, Age of Onset, Genetic Predisposition to Disease, Membrane Transport Proteins, DNA Repeat Expansion
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