Mitochondrial transcription factor A (TFAM) gene variation and risk of late-onset Alzheimer's disease
Open accessAbstract
Impaired mitochondrial function and an increased number of mutations in mitochondrial DNA (mtDNA) has been found in brains of patients with late-onset Alzheimer's disease (LOAD). The TFAM-gene encodes the mitochondrial transcription factor A, a protein that controls the transcription, replication, damage sensing, and repair of mtDNA. TFAM is on human chromosome region 10q21.1, where a locus for LOAD has been mapped. Our objective was to determine the role of TFAM-gene variation in the risk of LOAD. The seven TFAM coding exons were analysed through single strand conformation analysis and direct sequencing in a cohort of Spanish LOAD-patients and healthy controls. We found four common polymorphisms, two in the flanquing intronic and two in the coding sequences. Polymorphism rs1937 (+35 G/C) was the only missense change (S12T). Genotyping of this polymorphism in 300 LOAD-patients and 183 healthy controls showed a significantly higher frequency of GG-homozygotes in the patients (92% vs. 86%; p=0.04; OR=1.91, 95%CI=1.02-3.50). This suggests that S12 is a risk factor for LOAD in our population. In conclusion, rare variants (mutations) in the TFAM gene were not found in LOAD-patients, but the S12T polymorphism was a moderate risk factor for LOAD in our population.
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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 [168]
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“The missense polymorphism S12T has been found to be an AD risk factor in a Spanish population.(42) Thus, reduced expression may promote AD neuropathology.”
BackgroundMitochondrial dysfunction, cause or consequence in neurodegenerative diseases?
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“Mitochondrial dysfunction can occur as a result of the reduced capacity to produce ATP, and this impairment in energy supply can affect the function of neurons and other cells, increasing the risk for neurological disorders (Alvarez et al. 2008).”
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Mitochondriogenesis Genes and Extreme Longevity
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“…shown an association between rs1937 and neurodegenerative diseases characterized by disturbance of mtDNA integrity and mitochondrial dysfunction, i.e ., late-onset 36–38 or sporadic Alzheimer disease, 39 with the rare CC genotype conferring a protective effect 38 and the GG being a risk genotype.”
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“These studies indicated that the rare “CC genotype” of rs1937 was positively associated with late-onset AD [19, 21] while the “GG genotype” was a risk factor for AD [10, 21].”
ResultPolymorphisms of CHAT but not TFAM or VR22 are Associated with Alzheimer Disease Risk
Gao, L., Zhang, Y., Deng, J., Yu, W., & Yu, Y. (2016) · Medical Science Monitor · doi:10.12659/msm.895984 · Cited by 4 · see citing works
Polimorfismos no gene Tfam e características de carcaça em novilhas da raça Nelore
Ayres, D. R. (2008) · Americanae (AECID Library)
- Authors
- Alvarez, V., Corao, A. I., Alonso-Montes, C., Sánchez-Ferrero, E., De Mena, L., Morales, B., García-Castro, M., & Coto, E.
- Affiliations
- Genética Molecular, Hospital Universitario Central de Asturias, Oviedo, Spain
- Hospital Universitario Central de Asturias (ES)
- Venue
- Journal of Alzheimer s Disease
- Publisher
- SAGE Publications
- Published
- 2008-04-14
- Volume
- 13
- Issue
- 3
- Pages
- 275-280
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W71269467
- Cited by
- 27
- References
- 33
- Citations by year
- 2025: 1 · 2024: 1 · 2022: 1 · 2021: 1 · 2019: 1 · 2018: 1 · 2016: 4 · 2015: 1 · 2014: 1 · 2013: 3 · 2012: 1
- FWCI
- 2.48
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- cc-by-nc-nd
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Consultation of the Doctoral Thesis Database (TESEO) (Ministerio de Educación, Cultura y Deporte) (submittedVersion, cc-by-nc-nd)
- Funders
- European Regional Development Fund
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- TFAM
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Chromosomes, Human, Pair 10, DNA Mutational Analysis, DNA-Binding Proteins, DNA, Mitochondrial, Female, Genotype, Humans, Male, Middle Aged, Polymorphism, Genetic, Risk Factors, Transcription Factors, Genetic Variation, Cohort Studies, Point Mutation, DNA Primers, Mitochondrial Proteins
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