NR ANYY
AU Plamont,M.A.; Chasseigneaux,S.; Delasnerie-Laupretre,N.; Beaudry,P.; Peoc'h,K.; Laplanche,J.L.
TI Variation at the ADAM10 gene locus is not associated with Creutzfeldt-Jakob disease
QU Neuroscience Letters 2003 Jun 26; 344(2): 132-4
PT journal article
AB Prion diseases are characterized by the accumulation in the brain of a misfolded and protease-resistant form of the prion protein (PrPc). PrPc contains an amyloidogenic, neurotoxic sequence that is essential for conversion into PrPsc, the pathological isoform. During normal processing, PrPc is cleaved at a site within this sequence, and this cleavage is thought to destroy the amyloidogenic potential of the protein. ADAM10, a disintegrin and metalloprotease that plays a key role in the pathogenesis of Alzheimer's disease, was recently shown to use PrPc as a substrate. We investigated whether variability in the ADAM10 gene could contribute to the pathogenesis of Creutzfeldt-Jakob disease (CJD), by analyzing a single nucleotide polymorphism (SNP) within ADAM10, as a genetic marker potentially in linkage disequilibrium with a functional polymorphism, in patients with sporadic or variant CJD. We observed no significant differences in ADAM10 genotype or allele frequencies between CJD patients and healthy individuals. Moreover, the distribution of ADAM10 SNP genotypes and alleles did not differ between groups of patients based on genotype at the polymorphic codon 129 of the prion protein gene - the sole major genetic risk factor for CJD identified to date. Our data indicate that ADAM10 is unlikely to confer genetic susceptibility to CJD.
MH Adult; Aged; Aged, 80 and over; Creutzfeldt-Jakob Syndrome/*genetics; Genotype; Human; Membrane Proteins/*genetics; Metalloendopeptidases/*genetics; Middle Age; Polymorphism (Genetics); Risk Factors
AD Service de Biochimie et Biologie Moleculaire, Hopital Lariboisiere, AP-HP, and UPRES EA 3621 Biologie des Maladies a Prion et Regulations Cellulaires, Faculte des Sciences Pharmaceutiques et Biologiques, Paris, France.
SP englisch
PO Irland