Association of a polymorphism in mitochondrial transcription factor A (TFAM) with Parkinson's disease dementia but not dementia with Lewy bodies

Abstract The single nucleotide polymorphism (SNP) A > G rs2306604 in the gene encoding mitochondrial transcription factor A (TFAM) has been associated with Alzheimer's disease, with the A allele being recognised as a risk factor, but has not been studied in other types of dementia. We hypothesised that TFAM SNP rs2306604 might also be associated with Lewy body dementias. To test this hypothesis rs2306604 genotype was determined in 141 controls and 135 patients with dementia with Lewy bodies (DLB) or Parkinson's disease dementia (PDD). rs2306604 genotype frequencies were significantly different to controls in PDD ( p  = 0.042), but not in DLB ( p  = 0.529). The A allele was also associated with PDD ( p  = 0.024, OR = 2.092), but not DLB ( p  = 0.429, OR = 1.308). Moreover, the A allele was strongly associated with PDD in males ( p  = 0.001, OR = 5.570), but not in females ( p  = 0.832, OR = 1.100). Mitochondrial DNA copy number in the prefrontal cortex was also significantly reduced in PDD patients, but this reduction was not associated with rs2306604 genotype. These data show that the TFAM SNP rs2306604 A allele may be a risk factor for PDD, particularly in males, but not for DLB. Therefore, the genetic factors that predispose individuals to develop dementia may differ in PDD and DLB.