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 fact...Continue Reading
Citations
Nov 29, 2012·Rejuvenation Research·Catalina SantiagoAlejandro Lucia
Feb 18, 2016·Oxidative Medicine and Cellular Longevity·A DelbarbaD Uberti
Jul 30, 2015·Human Genetics·A J Rodriguez-AcevedoL R Griffiths
Sep 8, 2019·Translational Psychiatry·Gareth WilliamsClive Ballard
Jun 6, 2009·The FEBS Journal·Shangcheng XuZhengping Yu
Sep 10, 2011·Antioxidants & Redox Signaling·Russell H Swerdlow
Jun 18, 2016·Annals of Neurology·Jake G HoekstraScott R Kennedy
Aug 5, 2009·Human Genetics·Ildus I AhmetovViktor A Rogozkin
Mar 15, 2011·Alzheimer Disease and Associated Disorders·Edward C Lauterbach
Jun 9, 2016·Medical Science Monitor : International Medical Journal of Experimental and Clinical Research·Lili GaoYunxia Yu
Mar 1, 2016·Journal of Alzheimer's Disease : JAD·Alberto MontesantoGiuseppina Rose
Sep 6, 2014·Pharmaceuticals·Maja M GrabackaMalgorzata Pierzchalska
Jun 6, 2009·Ageing Research Reviews·Davide SeripaAlberto Pilotto
May 7, 2009·Experimental Neurology·Russell H Swerdlow, Shaharyar M Khan
Oct 28, 2010·Brain Research·Qun ZhangLan Tan