Exploring the association of glyceraldehyde-3-phosphate dehydrogenase gene and Alzheimer disease

Background: Previous linkage studies have shown that chromosome 12 harbors susceptibility genes for late-onset Alzheimer disease (LOAD). However, association studies of several candidate genes on this chromosome region have produced ambiguous results. A recent study reported the association between the glyceraldehyde-3-phosphate dehydrogenase (GAPD) gene on chromosome 12p and the risk of LOAD. Methods: The authors conducted family-based and case-control association studies in two independent LOAD data sets on 12 single-nucleotide polymorphisms (SNPs) in the GAPD gene and its paralogs. Results: No association was found of the GAPD gene with LOAD in the family-based data set, but marginal evidence of association was seen in the later-onset subgroup when age at onset was stratified. The SNP rs2029721 in one GAPD pseudogene was also found to be associated with risk for LOAD in the unrelated case-control data set (p = 0.003). Conclusions: The GAPD gene and its pseudogene may play a role in the development of late-onset Alzheimer disease. However, the effect, if any, is likely to be limited.

[1]  Demetrius M Maraganore,et al.  Blood is thicker than water , 2005, Neurology.

[2]  Mark Daly,et al.  Haploview: analysis and visualization of LD and haplotype maps , 2005, Bioinform..

[3]  Steven J. Schrodi,et al.  Association of late-onset Alzheimer's disease with genetic variation in multiple members of the GAPD gene family. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[4]  Hitoshi Takahashi,et al.  Disclosure of a pro-apoptotic glyceraldehyde-3-phosphate dehydrogenase promoter: anti-dementia drugs depress its activation in apoptosis. , 2004, Life sciences.

[5]  Eden R Martin,et al.  Accounting for linkage in family-based tests of association with missing parental genotypes. , 2003, American journal of human genetics.

[6]  D. Bennett,et al.  Alzheimer disease in the US population: prevalence estimates using the 2000 census. , 2003, Archives of neurology.

[7]  N. Laird,et al.  Estimation and Tests of Haplotype-Environment Interaction when Linkage Phase Is Ambiguous , 2003, Human Heredity.

[8]  Eden R Martin,et al.  Association study of Parkin gene polymorphisms with idiopathic Parkinson disease. , 2003, Archives of neurology.

[9]  L. Farrer,et al.  Identification of multiple loci for Alzheimer disease in a consanguineous Israeli-Arab community. , 2003, Human molecular genetics.

[10]  M. Owen,et al.  Full genome screen for Alzheimer disease: stage II analysis. , 2002, American journal of medical genetics.

[11]  D. Schaid,et al.  Score tests for association between traits and haplotypes when linkage phase is ambiguous. , 2002, American journal of human genetics.

[12]  V. D. Ramirez,et al.  Estradiol, in the CNS, targets several physiologically relevant membrane-associated proteins , 2001, Brain Research Reviews.

[13]  M. Owen,et al.  Susceptibility locus for Alzheimer's disease on chromosome 10. , 2000, Science.

[14]  P. M. Conneally,et al.  Identification of Novel Genes in Late-Onset Alzheimer's Disease , 2000, Experimental Gerontology.

[15]  E. Martin,et al.  A test for linkage and association in general pedigrees: the pedigree disequilibrium test. , 2000, American journal of human genetics.

[16]  J. Haines,et al.  Fine mapping of the chromosome 12 late-onset Alzheimer disease locus: potential genetic and phenotypic heterogeneity. , 2000, American journal of human genetics.

[17]  Gonçalo R. Abecasis,et al.  GOLD-Graphical Overview of Linkage Disequilibrium , 2000, Bioinform..

[18]  M. Owen,et al.  A full genome scan for late onset Alzheimer's disease , 1999 .

[19]  J. Hardy,et al.  Genetic classification of primary neurodegenerative disease. , 1998, Science.

[20]  A. Paterson,et al.  Evidence for an Alzheimer disease susceptibility locus on chromosome 12 and for further locus heterogeneity. , 1998, JAMA.

[21]  J. Haines,et al.  Complete Genomic Screen in Late-Onset Familial Alzheimer’s Disease , 1998, Neurobiology of Aging.

[22]  J. Haines,et al.  Complete genomic screen in late-onset familial Alzheimer disease. Evidence for a new locus on chromosome 12. , 1997, JAMA.

[23]  L. Friedhoff,et al.  The efficacy and safety of donepezil in patients with Alzheimer's disease: Results of a US multicentre, randomized, double-blind, placebo-controlled trial , 1996 .

[24]  M. Folstein,et al.  Alzheimer's disease in the National Academy of Sciences-National Research Council Registry of Aging Twin Veterans. III. Detection of cases, longitudinal results, and observations on twin concordance. , 1995, Archives of neurology.

[25]  C. Portera-Cailliau,et al.  Evidence for apoptotic cell death in Huntington disease and excitotoxic animal models , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[26]  C. Thompson,et al.  Apoptosis in the pathogenesis and treatment of disease , 1995, Science.

[27]  M. Rossor,et al.  Apolipoprotein E, epsilon 4 allele as a major risk factor for sporadic early and late-onset forms of Alzheimer's disease: analysis of the 19q13.2 chromosomal region. , 1994, Human molecular genetics.

[28]  J. Haines,et al.  Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. , 1993, Science.

[29]  H. Langen,et al.  Rat Brain Glyceraldehyde‐3‐Phosphate Dehydrogenase Interacts with the Recombinant Cytoplasmic Domain of Alzheimer's β‐Amyloid Precursor Protein , 1993, Journal of neurochemistry.

[30]  M. Pericak-Vance,et al.  Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage. , 1991, American journal of human genetics.

[31]  K. Davis,et al.  Familial aggregation in Alzheimer's disease , 1988, Neurology.

[32]  A. Kling,et al.  Oral tetrahydroaminoacridine in long-term treatment of senile dementia, Alzheimer type. , 1986, The New England journal of medicine.

[33]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[34]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.

[35]  P. Armitage.  Tests for Linear Trends in Proportions and Frequencies , 1955 .

[36]  J. Wesson Ashford,et al.  APOE genotype effects on alzheimer’s disease onset and epidemiology , 2007, Journal of Molecular Neuroscience.

[37]  M. Albert,et al.  Results of a high-resolution genome screen of 437 Alzheimer's disease families. , 2003, Human molecular genetics.

[38]  Pak Chung Sham,et al.  Genetic Power Calculator: design of linkage and association genetic mapping studies of complex traits , 2003, Bioinform..

[39]  W. Tatton,et al.  Reduced apoptosis after nerve growth factor and serum withdrawal: conversion of tetrameric glyceraldehyde-3-phosphate dehydrogenase to a dimer. , 2000, Molecular pharmacology.

[40]  L. Friedhoff,et al.  The efficacy and safety of donepezil in patients with Alzheimer's disease: results of a US Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial. The Donepezil Study Group. , 1996, Dementia.

[41]  M A Pericak-Vance,et al.  Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease. , 1993, Neurology.