TOMM40 polymorphisms in Italian Alzheimer's disease and frontotemporal dementia patients.

Chromosome 19 is one of the several prominent chromosomes related to the risk of developing late-onset Alzheimer's disease (LOAD) and frontotemporal lobar degeneration (FTLD). However, only Apolipoprotein E (APOE) has been confirmed as a risk factor for both disorders. The aim of this study was to investigate a set of polymorphisms in the translocase of the outer mitochondrial membrane 40 (TOMM40) gene, located in close proximity to APOE, to clarify if the TOMM40 gene may be considered a risk factor for AD and FTLD, independently of APOE status. We performed a case-control study in a dataset of Italian LOAD and FTLD patients, analyzing the following three single-nucleotide polymorphisms (SNPs): rs157580, rs2075650 and rs157581. The analysis was made in 710 Italian subjects: 282 LOAD patients, 156 FTLD patients and 272 healthy subjects. Our results confirm the presence of an association between TOMM40 SNPs and LOAD in our Italian population, suggesting that genetic variations proximate to APOE contributes to the LOAD risk. Genotype and allele distribution of the TOMM40 polymorphisms between the FTLD group and controls did not show any statistical difference. When we analyzed haplotype distribution of the SNPs, taking into account the presence of the APOE allele, we observed a strong association between the ε4 allele and the GAC haplotype both in LOAD and FTLD patients. In contrast, this association did not hold for ε3/GAC. These results demonstrate that the TOMM40 gene does not have an APOE-independent role in the risk of developing LOAD and FTLD.