UNC13A influences survival in Italian amyotrophic lateral sclerosis patients: A population-based study

Adriano Chiò, Gabriele Mora, Gabriella Restagno, Maura Brunetti, Irene Ossola, Marco Barberis, Luigi Ferrucci, Antonio Canosa, Umberto Manera, Cristina Moglia, Giuseppe Fuda, Bryan J. Traynor, Andrea Calvo

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
JournalNeurobiology of Aging
Volume34
Issue number1
DOIs
StatePublished - Jan 2013
Externally publishedYes

Keywords

  • Amyotrophic lateral sclerosis
  • Prognosis
  • Risk factor
  • UNC13A

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

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