An inherited variable poly-T repeat genotype in TOMM40 in Alzheimer disease.

Abstract

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.

• Authors: Allen D Roses
• Journal: Archives of neurology (Arch Neurol) Vol. 67 Issue 5 Pg. 536-41 (May 2010) ISSN: 1538-3687 [Electronic] United States
• PMID: 20457951 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Apolipoproteins E
• Membrane Transport Proteins
• Mitochondrial Precursor Protein Import Complex Proteins
• TOMM40 protein, human

Topics

• Age of Onset
• Alzheimer Disease (genetics, metabolism, physiopathology)
• Apolipoproteins E (genetics)
• Chromosomes, Human, Pair 19 (genetics)
• DNA Repeat Expansion (genetics)
• Gene Frequency (genetics)
• Genetic Predisposition to Disease (genetics)
• Humans
• Membrane Transport Proteins (genetics)
• Mitochondrial Precursor Protein Import Complex Proteins
• Polymorphism, Genetic (genetics)