Abstract
We investigated whether the C9orf72 repeat expansion is associated with specific clinical features, comorbidities, and prognosis in patients with amyotrophic lateral sclerosis (ALS). A cohort of 1417 ALS patients, diagnosed between January 1, 2009 and December 31, 2013 by 13 Italian ALS Referral Centers, was screened for the C9orf72 repeat expansion, and the analyses were performed comparing patients carrying this expansion (ALS-C9Pos) to those negative for this and other explored ALS-related mutations (ALS without genetic mutations, ALSwoGM). Compared to the ALSwoGM group, ALS-C9Pos patients (n = 84) were younger at disease onset, at the first clinical observation and at diagnosis (p < 0.001). After correcting for these differences, we found that ALS-C9Pos patients had higher odds of bulbar onset, diagnosis of frontotemporal dementia (FTD) and family history of ALS, FTD, and Alzheimer's disease and had lower odds of spinal onset, non-invasive ventilation, hypertension and psychiatric diseases than ALSwoGM patients. Among these variables, those related to shorter survival time were: bulbar onset, presence of FTD, hypertension, psychiatric disease, and family history of ALS (p < 0.05). Cox proportional hazards regression multivariate analysis suggested that carrying the C9orf72 repeat expansion was an independent factor negatively impacting on survival time in men (HR 1.58, 95% CI 1.07-2.33, p = 0.021), but not in women (p > 0.05) as well as in the whole sample (p > 0.05). When compared to ALSwoGM, ALS-C9Pos showed an earlier disease onset, no significant diagnostic delay and a higher odds of bulbar onset, FTD and family history of ALS and dementia. Moreover, male sex drove the negative effect of expanded variant on survival, confirming the hypothesis that sex is likely to be a crucial factor in the biology of C9orf72-related disease.
| Original language | English |
|---|---|
| Article number | 485 |
| Journal | Frontiers in Neuroscience |
| Volume | 13 |
| Issue number | MAY |
| DOIs | |
| Publication status | Published - Jan 1 2019 |
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Keywords
- Amyotrophic lateral sclerosis
- C9orf72 expansion
- Comorbidity
- Gender
- Survival
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Comparative analysis of C9Orf72 and sporadic disease in a large multicenter ALS population : The effect of Male sex on survival of C9Orf72 positive patients. / Trojsi, Francesca; Siciliano, Mattia; Femiano, Cinzia; Santangelo, Gabriella; Lunetta, Christian; Calvo, Andrea; Moglia, Cristina; Marinou, Kalliopi; Ticozzi, Nicola; Ferro, Christian; Scialò, Carlo; Sorarù, Gianni; Conte, Amelia; Falzone, Yuri M.; Tortelli, Rosanna; Russo, Massimo; Sansone, Valeria Ada; Chiò, Adriano; Mora, Gabriele; Silani, Vincenzo; Volanti, Paolo; Caponnetto, Claudia; Querin, Giorgia; Sabatelli, Mario; Riva, Nilo; Logroscino, Giancarlo; Messina, Sonia; Fasano, Antonio; Monsurrò, Maria Rosaria; Tedeschi, Gioacchino; Mandrioli, Jessica.
In: Frontiers in Neuroscience, Vol. 13, No. MAY, 485, 01.01.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Comparative analysis of C9Orf72 and sporadic disease in a large multicenter ALS population
T2 - The effect of Male sex on survival of C9Orf72 positive patients
AU - Trojsi, Francesca
AU - Siciliano, Mattia
AU - Femiano, Cinzia
AU - Santangelo, Gabriella
AU - Lunetta, Christian
AU - Calvo, Andrea
AU - Moglia, Cristina
AU - Marinou, Kalliopi
AU - Ticozzi, Nicola
AU - Ferro, Christian
AU - Scialò, Carlo
AU - Sorarù, Gianni
AU - Conte, Amelia
AU - Falzone, Yuri M.
AU - Tortelli, Rosanna
AU - Russo, Massimo
AU - Sansone, Valeria Ada
AU - Chiò, Adriano
AU - Mora, Gabriele
AU - Silani, Vincenzo
AU - Volanti, Paolo
AU - Caponnetto, Claudia
AU - Querin, Giorgia
AU - Sabatelli, Mario
AU - Riva, Nilo
AU - Logroscino, Giancarlo
AU - Messina, Sonia
AU - Fasano, Antonio
AU - Monsurrò, Maria Rosaria
AU - Tedeschi, Gioacchino
AU - Mandrioli, Jessica
PY - 2019/1/1
Y1 - 2019/1/1
N2 - We investigated whether the C9orf72 repeat expansion is associated with specific clinical features, comorbidities, and prognosis in patients with amyotrophic lateral sclerosis (ALS). A cohort of 1417 ALS patients, diagnosed between January 1, 2009 and December 31, 2013 by 13 Italian ALS Referral Centers, was screened for the C9orf72 repeat expansion, and the analyses were performed comparing patients carrying this expansion (ALS-C9Pos) to those negative for this and other explored ALS-related mutations (ALS without genetic mutations, ALSwoGM). Compared to the ALSwoGM group, ALS-C9Pos patients (n = 84) were younger at disease onset, at the first clinical observation and at diagnosis (p < 0.001). After correcting for these differences, we found that ALS-C9Pos patients had higher odds of bulbar onset, diagnosis of frontotemporal dementia (FTD) and family history of ALS, FTD, and Alzheimer's disease and had lower odds of spinal onset, non-invasive ventilation, hypertension and psychiatric diseases than ALSwoGM patients. Among these variables, those related to shorter survival time were: bulbar onset, presence of FTD, hypertension, psychiatric disease, and family history of ALS (p < 0.05). Cox proportional hazards regression multivariate analysis suggested that carrying the C9orf72 repeat expansion was an independent factor negatively impacting on survival time in men (HR 1.58, 95% CI 1.07-2.33, p = 0.021), but not in women (p > 0.05) as well as in the whole sample (p > 0.05). When compared to ALSwoGM, ALS-C9Pos showed an earlier disease onset, no significant diagnostic delay and a higher odds of bulbar onset, FTD and family history of ALS and dementia. Moreover, male sex drove the negative effect of expanded variant on survival, confirming the hypothesis that sex is likely to be a crucial factor in the biology of C9orf72-related disease.
AB - We investigated whether the C9orf72 repeat expansion is associated with specific clinical features, comorbidities, and prognosis in patients with amyotrophic lateral sclerosis (ALS). A cohort of 1417 ALS patients, diagnosed between January 1, 2009 and December 31, 2013 by 13 Italian ALS Referral Centers, was screened for the C9orf72 repeat expansion, and the analyses were performed comparing patients carrying this expansion (ALS-C9Pos) to those negative for this and other explored ALS-related mutations (ALS without genetic mutations, ALSwoGM). Compared to the ALSwoGM group, ALS-C9Pos patients (n = 84) were younger at disease onset, at the first clinical observation and at diagnosis (p < 0.001). After correcting for these differences, we found that ALS-C9Pos patients had higher odds of bulbar onset, diagnosis of frontotemporal dementia (FTD) and family history of ALS, FTD, and Alzheimer's disease and had lower odds of spinal onset, non-invasive ventilation, hypertension and psychiatric diseases than ALSwoGM patients. Among these variables, those related to shorter survival time were: bulbar onset, presence of FTD, hypertension, psychiatric disease, and family history of ALS (p < 0.05). Cox proportional hazards regression multivariate analysis suggested that carrying the C9orf72 repeat expansion was an independent factor negatively impacting on survival time in men (HR 1.58, 95% CI 1.07-2.33, p = 0.021), but not in women (p > 0.05) as well as in the whole sample (p > 0.05). When compared to ALSwoGM, ALS-C9Pos showed an earlier disease onset, no significant diagnostic delay and a higher odds of bulbar onset, FTD and family history of ALS and dementia. Moreover, male sex drove the negative effect of expanded variant on survival, confirming the hypothesis that sex is likely to be a crucial factor in the biology of C9orf72-related disease.
KW - Amyotrophic lateral sclerosis
KW - C9orf72 expansion
KW - Comorbidity
KW - Gender
KW - Survival
UR - http://www.scopus.com/inward/record.url?scp=85068535656&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068535656&partnerID=8YFLogxK
U2 - 10.3389/fnins.2019.00485
DO - 10.3389/fnins.2019.00485
M3 - Article
AN - SCOPUS:85068535656
VL - 13
JO - Frontiers in Neuroscience
JF - Frontiers in Neuroscience
SN - 1662-4548
IS - MAY
M1 - 485
ER -