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


Journal Article (Review)

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.

Full Text

Cited Authors

  • Roses, AD

Published Date

  • May 2010

Published In

Volume / Issue

  • 67 / 5

Start / End Page

  • 536 - 541

PubMed ID

  • 20457951

Pubmed Central ID

  • 20457951

Electronic International Standard Serial Number (EISSN)

  • 1538-3687

International Standard Serial Number (ISSN)

  • 0003-9942

Digital Object Identifier (DOI)

  • 10.1001/archneurol.2010.88


  • eng