title: UNC13A influences survival in Italian amyotrophic lateral sclerosis patients: a population-based study.
abstract: The common variant rs12608932, located within an intron of UNC13A gene on chromosome 19p13.3, has been suggested to influence susceptibility to amyotrophic lateral sclerosis (ALS), as well as survival, in patients of north European descent. To examine this possibility further, we evaluated the association of rs12608932 with susceptibility and survival in a population-based cohort of 500 Italian ALS patients and 1457 Italian control samples. Although rs12608932 was not associated with ALS susceptibility in our series (p = 0.124), it was significantly associated with survival under the recessive model (median survival for AA/AC genotypes = 3.5 years [interquartile range, 2.2-6.4]; CC = 2.5 years [interquartile range, 1.6-4.2]; p = 0.017). Furthermore, rs12608932 genotype remained an independent prognostic factor in Cox multivariable analysis adjusting for other factors known to influence survival (p = 0.023). Overall, minor allele carrier status of rs12608932 was strongly associated with an approximate 1-year reduction of survival in ALS patients, making it a significant determinant of phenotype variation. The identification of UNC13A as a modifier of prognosis among sporadic ALS patients potentially provides a new therapeutic target aimed at slowing disease progression.
authors.affiliation: ALS Center, Department of Neuroscience, University of Torino, and Azienda Ospedale Università San Giovanni Battista, Torino, Italy. achio@usa.net
authors.forename: Adriano
authors.initials: A
authors.lastname: Chiò
authors.forename: Gabriele
authors.initials: G
authors.lastname: Mora
authors.forename: Gabriella
authors.initials: G
authors.lastname: Restagno
authors.forename: Maura
authors.initials: M
authors.lastname: Brunetti
authors.forename: Irene
authors.initials: I
authors.lastname: Ossola
authors.forename: Marco
authors.initials: M
authors.lastname: Barberis
authors.forename: Luigi
authors.initials: L
authors.lastname: Ferrucci
authors.forename: Antonio
authors.initials: A
authors.lastname: Canosa
authors.forename: Umberto
authors.initials: U
authors.lastname: Manera
authors.forename: Cristina
authors.initials: C
authors.lastname: Moglia
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Fuda
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Traynor
authors.forename: Andrea
authors.initials: A
authors.lastname: Calvo
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology / Q000235:genetics / Q000401:mortality; D000073885:C9orf72 Protein; D016009:Chi-Square Distribution; D018672:Community Health Planning; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: D000073885:C9orf72 Protein; C568651:C9orf72 protein, human; D009419:Nerve Tissue Proteins; D011506:Proteins; C485548:UNC13B protein, human