Günther Claudia, von Hadeln Kirsten, Müller-Thomsen Tomas, Alberici Antonella, Binetti Giuliano, Hock Christoph, Nitsch Roger M, Stoppe Gabriela, Reiss Jochen, Gal Andreas, Finckh Ulrich
Department of Human Genetics, University Hospital Hamburg-Eppendorf, Butenfeld 42, 22529 Hamburg, Germany.
Neurosci Lett. 2004 Oct 21;369(3):219-23. doi: 10.1016/j.neulet.2004.07.070.
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.
线粒体转录因子A（TFAM）对于哺乳动物线粒体DNA（mtDNA）的转录和复制至关重要。mtDNA完整性维持或线粒体功能的紊乱可能是诸如阿尔茨海默病（AD）等神经退行性疾病的基础。TFAM，编码TFAM的基因定位于染色体10q21.1，在多个研究样本中该区域显示与晚发型AD存在连锁关系。我们在372例AD患者和295例非痴呆对照受试者中筛选了TFAM的单核苷酸多态性（SNP），并对TFAM线粒体信号序列中编码S12T的G>C SNP rs1937以及A>G SNP rs2306604（IVS4+113A>G）进行了基因分型。基因型rs1937G/G与女性AD存在关联，并且在整个样本以及女性中，一种TFAM单倍型与AD存在关联。这些发现表明，包含rs1937 G（对应S12）的TFAM单倍型可能是AD的一个中度风险因素。
