The cis-regulatory effect of an Alzheimer’s disease-associated poly-T locus on expression of TOMM40 and apolipoprotein E genes

We investigated the genomic region spanning the Translocase of the Outer Mitochondrial Membrane 40‐kD (TOMM40) and Apolipoprotein E (APOE) genes, that has been associated with the risk and age of onset of late‐onset Alzheimer's disease (LOAD) to determine whether a highly polymorphic, intronic poly‐T within this region (rs10524523; hereafter, 523) affects expression of the APOE and TOMM40 genes. Alleles of this locus are classified as S, short; L, long; and VL, very long based on the number of T residues.

[1]  J. Widom,et al.  Poly(dA-dT) Promoter Elements Increase the Equilibrium Accessibility of Nucleosomal DNA Target Sites , 2001, Molecular and Cellular Biology.

[2]  H. Anandatheerthavarada,et al.  Mitochondrial trafficking of APP and alpha synuclein: Relevance to mitochondrial dysfunction in Alzheimer's and Parkinson's diseases. , 2010, Biochimica et biophysica acta.

[3]  L. Bekris,et al.  Functional Analysis of APOE Locus Genetic Variation Implicates Regional Enhancers in the Regulation of Both TOMM40 and APOE , 2011, Journal of Human Genetics.

[4]  R. Swerdlow,et al.  The Alzheimer's disease mitochondrial cascade hypothesis. , 2010, Journal of Alzheimer's disease : JAD.

[5]  A. Roses,et al.  A homopolymer polymorphism in the TOMM40 gene contributes to cognitive performance in aging , 2012, Alzheimer's & Dementia.

[6]  David M Holtzman,et al.  Association and expression analyses with single-nucleotide polymorphisms in TOMM40 in Alzheimer disease. , 2011, Archives of neurology.

[7]  T. Rudel,et al.  Conserved roles of Sam50 and metaxins in VDAC biogenesis , 2007, EMBO reports.

[8]  A. Pfeufer,et al.  TaqMan Systems for Genotyping of Disease-Related Polymorphisms Present in the Gene Encoding Apolipoprotein E , 2002, Clinical chemistry and laboratory medicine.

[9]  Paul K Crane,et al.  Comprehensive search for Alzheimer disease susceptibility loci in the APOE region. , 2012, Archives of neurology.

[10]  Krzysztof Safranow,et al.  TOMM40 rs10524523 polymorphism's role in late-onset Alzheimer's disease and in longevity. , 2012, Journal of Alzheimer's disease : JAD.

[11]  A. Roses,et al.  TOMM40, APOE, and age of onset of Alzheimer's disease , 2010, Alzheimer's & Dementia.

[12]  Robert C. Green,et al.  The effect of TOMM40 poly-T length on gray matter volume and cognition in middle-aged persons with APOE ɛ3/ɛ3 genotype , 2011, Alzheimer's & Dementia.

[13]  B. Winblad,et al.  The amyloid β-peptide is imported into mitochondria via the TOM import machinery and localized to mitochondrial cristae , 2008, Proceedings of the National Academy of Sciences.

[14]  A D Roses,et al.  A TOMM40 variable-length polymorphism predicts the age of late-onset Alzheimer's disease , 2009, The Pharmacogenomics Journal.

[15]  K. Krishnan,et al.  Downregulation of TOMM40 expression in the blood of Alzheimer disease subjects compared with matched controls. , 2012, Journal of psychiatric research.

[16]  A. Roses,et al.  Using Genetics to Enable Studies on the Prevention of Alzheimer's Disease , 2013, Clinical pharmacology and therapeutics.

[17]  J. Nierenberg,et al.  Cerebrospinal fluid cortisol concentrations in healthy elderly are affected by both APOE and TOMM40 variants , 2012, Psychoneuroendocrinology.

[18]  Michael W. Lutz,et al.  Levels of cerebrospinal fluid neurofilament light protein in healthy elderly vary as a function of TOMM40 variants , 2012, Experimental Gerontology.

[19]  A. Singleton,et al.  The law of mass action applied to neurodegenerative disease: a hypothesis concerning the etiology and pathogenesis of complex diseases. , 2004, Human molecular genetics.

[20]  R. Swerdlow.  Mitochondria and cell bioenergetics: increasingly recognized components and a possible etiologic cause of Alzheimer's disease. , 2012, Antioxidants & redox signaling.

[21]  K. Roeder,et al.  TOMM40 poly-T repeat lengths, age of onset and psychosis risk in Alzheimer disease , 2011, Neurobiology of Aging.

[22]  A. Roses,et al.  Genetic variation at a single locus and age of onset for Alzheimer's disease , 2010, Alzheimer's & Dementia.

[23]  A. Roses,et al.  TOMM40 and APOE: Requirements for replication studies of association with age of disease onset and enrichment of a clinical trial , 2013, Alzheimer's & Dementia.

[24]  P. Reddy,et al.  Impaired mitochondrial dynamics and abnormal interaction of amyloid beta with mitochondrial protein Drp1 in neurons from patients with Alzheimer's disease: implications for neuronal damage. , 2011, Human molecular genetics.

[25]  C. Graff,et al.  Biochemical studies of poly-T variants in the Alzheimer's disease associated TOMM40 gene. , 2012, Journal of Alzheimer's disease : JAD.

[26]  P. Rorsman,et al.  Gene expression profiling in single cells from the pancreatic islets of Langerhans reveals lognormal distribution of mRNA levels. , 2005, Genome research.

[27]  J. Victoroff,et al.  Increased Apolipoprotein E mRNA in the Hippocampus in Alzheimer Disease and in Rats after Entorhinal Cortex Lesioning , 1998, Experimental Neurology.

[28]  E. Segal,et al.  Poly(da:dt) Tracts: Major Determinants of Nucleosome Organization This Review Comes from a Themed Issue on Protein-nucleic Acid Interactions Edited , 2022 .

[29]  A. Roses,et al.  Characterization of the Poly-T Variant in the TOMM40 Gene in Diverse Populations , 2012, PloS one.

[30]  P. Hof,et al.  Association of ApoE and LRP mRNA levels with dementia and AD neuropathology , 2012, Neurobiology of Aging.

[31]  B. Hyman,et al.  Expression of APP pathway mRNAs and proteins in Alzheimer’s disease , 2007, Brain Research.