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.
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Polymorphisms in TFAM associate with AD risk in some studies.
“Polymorphisms in other nuclear genes, for example transcription factor A of the mitochondria (TFAM), associate with AD risk in some studies [168-170].”
From The Alzheimer’s disease mitochondrial cascade hypothesis: progress and perspectives (2014) · cites this paper as [169]
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- Authors
- Belin, A. C., Björk, B. F., Westerlund, M., Galter, D., Sydow, O., Lind, C., Pernold, K., Rosvall, L., Håkansson, A., Winblad, B., Nissbrandt, H., Graff, C., & Olson, L.
- Affiliations
- Karolinska University Hospital (SE)
- Karolinska Institutet (SE)
- University of Gothenburg (SE)
- Corresponding author
- Belin, Andrea Carmine
- ORCID
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 2007-06
- Volume
- 420
- Issue
- 3
- Pages
- 257-262
- ISSN
- 0304-3940 (ISSN-L)
- OpenAlex
- W1992207511
- Cited by
- 48
- References
- 48
- Citations by year
- 2025: 4 · 2024: 1 · 2022: 1 · 2021: 3 · 2019: 1 · 2018: 3 · 2017: 4 · 2016: 6 · 2014: 3 · 2013: 4
- FWCI
- 3.35
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Stiftelsen för Gamla Tjänarinnor
- Vetenskapsrådet
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Keywords
- TFAM, Alzheimer's disease, Parkinson's disease, genetic association, mitochondrial dysfunction, mitochondrial DNA copy number, haplotype association, genetic risk factors
- MeSH terms
- Aged, Alleles, Alzheimer Disease, DNA, DNA-Binding Proteins, Female, Gene Frequency, Genotype, Haplotypes, Humans, Male, Middle Aged, Parkinson Disease, Sweden, Transcription Factors, Genetic Variation, Reverse Transcriptase Polymerase Chain Reaction, Mitochondrial Proteins
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