An inherited variable poly-T repeat genotype in TOMM40 in Alzheimer disease.
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.
Roses
Allen D
AD
Department of Neurobiology and Neurology and the Deane Drug Discovery Institute, Duke University, Durham, North Carolina 27708, USA. allen.roses@duke.edu
D017668:Age of Onset; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D001057:Apolipoproteins E / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D042622:DNA Repeat Expansion / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics*; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D011110:Polymorphism, Genetic / Q000235:genetics*
D001057:Apolipoproteins E; D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; C400783:TOMM40 protein, human
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