title: Association study of two genetic variants in mitochondrial transcription factor A (TFAM) in Alzheimer's and Parkinson's disease.
abstract: Mitochondrial (mt) dysfunction has been implicated in Alzheimer's (AD) and Parkinson's disease (PD). Mitochondrial transcription factor A (TFAM) is needed for mtDNA maintenance, regulating mtDNA copy number and is absolutely required for transcriptional initiation at mtDNA promoters. Two genetic variants in TFAM have been reported to be associated with AD in a Caucasian case-control material collected from Germany, Switzerland and Italy. One of these variants was reported to show a tendency for association with AD in a pooled Scottish and Swedish case-control material and the other variant was reported to be associated with AD in a recent meta-analysis. We investigated these two genetic variants, rs1937 and rs2306604, in an AD and a PD case-control material, both from Sweden and found significant genotypic as well as allelic association to marker rs2306604 in the AD case-control material (P=0.05 and P=0.03, respectively), where the A-allele appears to increase risk for developing AD. No association was observed for marker rs1937. We did not find any association in the PD case-control material for either of the two markers. The distribution of the two-locus haplotype frequencies (based on rs1937 and rs2306604) did not differ significantly between affected individuals and controls in the two sample sets. However, the global P-value for haplotypic association testing indicated borderline association in the AD sample set. Our data suggests that the rs2306604 A-allele could be a moderate risk factor for AD, which is supported by the recent meta-analysis.
authors.affiliation: Department of Neuroscience, Karolinska Institutet, and Karolinska University Hospital, Stockholm, Sweden. Andrea.Carmine.Belin@ki.se
authors.forename: Andrea Carmine
authors.initials: AC
authors.lastname: Belin
authors.forename: Behnosh F
authors.initials: BF
authors.lastname: Björk
authors.forename: Marie
authors.initials: M
authors.lastname: Westerlund
authors.forename: Dagmar
authors.initials: D
authors.lastname: Galter
authors.forename: Olof
authors.initials: O
authors.lastname: Sydow
authors.forename: Charlotta
authors.initials: C
authors.lastname: Lind
authors.forename: Karin
authors.initials: K
authors.lastname: Pernold
authors.forename: Lina
authors.initials: L
authors.lastname: Rosvall
authors.forename: Anna
authors.initials: A
authors.lastname: Håkansson
authors.forename: Bengt
authors.initials: B
authors.lastname: Winblad
authors.forename: Hans
authors.initials: H
authors.lastname: Nissbrandt
authors.forename: Caroline
authors.initials: C
authors.lastname: Graff
authors.forename: Lars
authors.initials: L
authors.lastname: Olson
mesh_terms: D000368:Aged; D000483:Alleles; D000544:Alzheimer Disease / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D010300:Parkinson Disease / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013548:Sweden; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; C499631:TFAM protein, human; D014157:Transcription Factors; D004247:DNA