TY - JOUR
T1 - UNC13A influences survival in Italian amyotrophic lateral sclerosis patients
T2 - A population-based study
AU - Chiò, Adriano
AU - Mora, Gabriele
AU - Restagno, Gabriella
AU - Brunetti, Maura
AU - Ossola, Irene
AU - Barberis, Marco
AU - Ferrucci, Luigi
AU - Canosa, Antonio
AU - Manera, Umberto
AU - Moglia, Cristina
AU - Fuda, Giuseppe
AU - Traynor, Bryan J.
AU - Calvo, Andrea
PY - 2013/1
Y1 - 2013/1
N2 - 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.
AB - 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.
KW - Amyotrophic lateral sclerosis
KW - Prognosis
KW - Risk factor
KW - UNC13A
UR - http://www.scopus.com/inward/record.url?scp=84868096807&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84868096807&partnerID=8YFLogxK
U2 - 10.1016/j.neurobiolaging.2012.07.016
DO - 10.1016/j.neurobiolaging.2012.07.016
M3 - Article
C2 - 22921269
AN - SCOPUS:84868096807
SN - 0197-4580
VL - 34
JO - Neurobiology of Aging
JF - Neurobiology of Aging
IS - 1
ER -