A variable-length poly-T variant in intron 6 of the TOMM40 gene, rs10524523, is associated with risk and age-of-onset of sporadic (late-onset) Alzheimer's disease.
The very long (VL) poly-T variant at rs10524523 ("523") of the TOMM40 gene may hasten the onset of late-onset Alzheimer's disease (LOAD) and induce more profound cognitive impairment compared with the short (S) poly-T variant.
We investigated the genomic region spanning the Translocase of the Outer Mitochondrial Membrane 40-kD (TOMM40) and Apolipoprotein E (APOE) genes, that has been associated with the risk and age of onset of late-onset Alzheimer's disease (LOAD) to determine whether a highly polymorphic, intronic poly-T within this region (rs10524523; hereafter, 523) affects expression of the APOE and TOMM40 genes.
We conclude that in the carriers of TOMM40-APOE haplotypes comprising E4 allele, the TOMM40 rs10524523 allele does not play substantial role in establishing LOAD risk.
A variable poly-T length polymorphism at rs10524523, within intron 6 of the translocase of the outer mitochondrial membrane (TOMM40) gene, has been shown to influence age of onset in LOAD, with very long (VL) poly-T length associated with earlier disease onset, and short poly-T length associated with later onset.
We found a significant association between rs10524523 and risk of LOAD in APOE 33 homozygotes but in the opposite direction as the previously reported association (the very long allele was underrepresented in cases vs controls in this study (P = .004]).