title: Mitochondrial transcription factor A (TFAM) gene variation and risk of late-onset Alzheimer's disease.
abstract: 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.
authors.affiliation: Genética Molecular, Hospital Universitario Central de Asturias, Oviedo, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Alvarez
authors.forename: Ana I
authors.initials: AI
authors.lastname: Corao
authors.forename: Cristina
authors.initials: C
authors.lastname: Alonso-Montes
authors.forename: Elena
authors.initials: E
authors.lastname: Sánchez-Ferrero
authors.forename: Lorena
authors.initials: L
authors.lastname: De Mena
authors.forename: Blanca
authors.initials: B
authors.lastname: Morales
authors.forename: Mónica
authors.initials: M
authors.lastname: García-Castro
authors.forename: Eliecer
authors.initials: E
authors.lastname: Coto
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics*; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D017354:Point Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics; D012307:Risk Factors; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D017931:DNA Primers; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D014157:Transcription Factors; C422562:mitochondrial transcription factor A