title: Association study of the ubiquitin conjugating enzyme gene UBE2H in sporadic ALS.
abstract: Ubiquitin inclusions represent a cytopathological hallmark of ALS. The ubiquitin-dependent protein degradation pathway may also be involved in the pathophysiology of SOD1 mutated ALS cases as demonstrated in transgenic animals. UBE2H is an ubiquitin conjugating enzyme known to act on histones and cytoskeletal proteins, both involved in the degenerative pathway of the motor neuron. We screened the whole coding sequence of the UBE2H gene in 24 sporadic ALS (SALS) patients using single strand conformation polymorphism (SSCP). All variants detected by SSCP were analysed by genomic DNA sequencing. We found one known polymorphism (rs12539800) and two new synonymous single nucleotide polymorphisms (SNP) (nG78A and nG501A). The allele distribution of the rs12539800 (A336G) SNP were tested for association in 252 SALS patients and 357 controls. The allele and genotype distributions were identical in the two groups. The UBE2H gene is not implicated in SALS; however, the ubiquitin pathway is worthy of further investigation in ALS.
authors.affiliation: INSERM U930, Université François Rabelais Tours, Montpellier, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Martin
authors.forename: Patrick
authors.initials: P
authors.lastname: Vourc'h
authors.forename: Marie
authors.initials: M
authors.lastname: Mahé
authors.forename: Rose-Anne
authors.initials: RA
authors.lastname: Thépault
authors.forename: Catherine
authors.initials: C
authors.lastname: Antar
authors.forename: Sylviane
authors.initials: S
authors.lastname: Védrine
authors.forename: Julien
authors.initials: J
authors.lastname: Praline
authors.forename: William
authors.initials: W
authors.lastname: Camu
authors.forename: Christian R
authors.initials: CR
authors.lastname: Andres
authors.forename: Philippe
authors.initials: P
authors.lastname: Corcia
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000503:physiopathology; D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D004252:DNA Mutational Analysis; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D018807:Polymorphism, Single-Stranded Conformational; D017422:Sequence Analysis, DNA; D025801:Ubiquitin / Q000378:metabolism; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics*
chemical_list: D025801:Ubiquitin; C086376:UBE2H protein, human; D044763:Ubiquitin-Conjugating Enzymes