Possible association of mitochondrial transcription factor A (TFAM) genotype with sporadic Alzheimer disease.
Mitochondrial transcription factor A (TFAM) is essential for transcription and replication of mammalian mitochondrial DNA (mtDNA). Disturbance of maintenance of mtDNA integrity or mitochondrial function may underlay neurodegenerative disorders such as Alzheimer disease (AD). TFAM, the gene encoding TFAM maps to chromosome 10q21.1, a region that showed linkage to late-onset AD in several study samples. We screened TFAM for single nucleotide polymorphisms (SNPs) and genotyped the G>C SNP rs1937, coding for S12T in mitochondrial signal sequence of TFAM, and the A>G SNP rs2306604 (IVS4+113A>G) in 372 AD patients and 295 nondemented control subjects. There was an association of genotype rs1937G/G with AD in females and an association of a TFAM haplotype with AD both in the whole sample and in females. The findings suggest that a TFAM haplotype containing rs1937 G (for S12) may be a moderate risk factor for AD.
Department of Human Genetics, University Hospital Hamburg-Eppendorf, Butenfeld 42, 22529 Hamburg, Germany.
Claudia
C
Günther
Kirsten
K
von Hadeln
Tomas
T
Müller-Thomsen
Antonella
A
Alberici
Giuliano
G
Binetti
Christoph
C
Hock
Roger M
RM
Nitsch
Gabriela
G
Stoppe
Jochen
J
Reiss
Andreas
A
Gal
Ulrich
U
Finckh
D000544:Alzheimer Disease / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D024101:Mitochondrial Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods; D012737:Sex Factors; D014157:Transcription Factors / Q000235:genetics*
D001057:Apolipoproteins E; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D009687:Nuclear Proteins; C499631:TFAM protein, human; D014157:Transcription Factors; C422562:mitochondrial transcription factor A