Abstract
Amyotrophic lateral sclerosis (ALS) is a multifactorial disease, possibly with contributions from genetics and lifestyle. We examined variants in genes relevant to energy metabolism and physical activity in a case-control association study, with the aim of assessing genetics and physical activity as contributors to ALS risk. A well-characterized sample of Italian ALS patients (101) and controls (101) from the EURALS Consortium underwent a questionnaire interview on demographic, physical and other lifestyle habits, and venipuncture for DNA extraction. The genes selected were sirtuin 3 (SIRT3), peroxisome proliferator-activated receptor-γ coactivator-1α (PPARGC1A) and apolipoprotein E (APOE). Genetic studies suggested, for the first time, a protective role of the SIRT3 single-nucleotide polymorphism rs4980329 in ALS risk, and a contribution of the APOE-ε2 allele, which was more frequent in ALS patients than in controls. A joint analysis coupling genetic data and sporting activity revealed opposite roles of APOE-ε2 and SIRT3 rs3825075, the former being more frequent in physically active ALS patients and the latter more frequent in physically inactive patients. These findings suggest a contribution to ALS risk of genetic and environmental factors involved in energy metabolism, and stress the importance of a multifactorial analysis for evaluating this risk.
| Original language | English |
|---|---|
| Pages (from-to) | 301-309 |
| Number of pages | 9 |
| Journal | Genes and Genetic Systems |
| Volume | 91 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jan 1 2017 |
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Keywords
- Amyotrophic lateral sclerosis
- Apolipoprotein E
- Physical activity
- PPARGC1A
- Sirtuin 3
ASJC Scopus subject areas
- Molecular Biology
- Genetics
Cite this
The role of single-nucleotide variants of the energy metabolism-linked genes SIRT3, PPARGC1A and APOE in amyotrophic lateral sclerosis risk. / Albani, Diego; Pupillo, Elisabetta; Bianchi, Elisa; Chierchia, Armando; Martines, Rosalba; Forloni, Gianluigi; Beghi, Ettore.
In: Genes and Genetic Systems, Vol. 91, No. 6, 01.01.2017, p. 301-309.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The role of single-nucleotide variants of the energy metabolism-linked genes SIRT3, PPARGC1A and APOE in amyotrophic lateral sclerosis risk
AU - Albani, Diego
AU - Pupillo, Elisabetta
AU - Bianchi, Elisa
AU - Chierchia, Armando
AU - Martines, Rosalba
AU - Forloni, Gianluigi
AU - Beghi, Ettore
PY - 2017/1/1
Y1 - 2017/1/1
N2 - Amyotrophic lateral sclerosis (ALS) is a multifactorial disease, possibly with contributions from genetics and lifestyle. We examined variants in genes relevant to energy metabolism and physical activity in a case-control association study, with the aim of assessing genetics and physical activity as contributors to ALS risk. A well-characterized sample of Italian ALS patients (101) and controls (101) from the EURALS Consortium underwent a questionnaire interview on demographic, physical and other lifestyle habits, and venipuncture for DNA extraction. The genes selected were sirtuin 3 (SIRT3), peroxisome proliferator-activated receptor-γ coactivator-1α (PPARGC1A) and apolipoprotein E (APOE). Genetic studies suggested, for the first time, a protective role of the SIRT3 single-nucleotide polymorphism rs4980329 in ALS risk, and a contribution of the APOE-ε2 allele, which was more frequent in ALS patients than in controls. A joint analysis coupling genetic data and sporting activity revealed opposite roles of APOE-ε2 and SIRT3 rs3825075, the former being more frequent in physically active ALS patients and the latter more frequent in physically inactive patients. These findings suggest a contribution to ALS risk of genetic and environmental factors involved in energy metabolism, and stress the importance of a multifactorial analysis for evaluating this risk.
AB - Amyotrophic lateral sclerosis (ALS) is a multifactorial disease, possibly with contributions from genetics and lifestyle. We examined variants in genes relevant to energy metabolism and physical activity in a case-control association study, with the aim of assessing genetics and physical activity as contributors to ALS risk. A well-characterized sample of Italian ALS patients (101) and controls (101) from the EURALS Consortium underwent a questionnaire interview on demographic, physical and other lifestyle habits, and venipuncture for DNA extraction. The genes selected were sirtuin 3 (SIRT3), peroxisome proliferator-activated receptor-γ coactivator-1α (PPARGC1A) and apolipoprotein E (APOE). Genetic studies suggested, for the first time, a protective role of the SIRT3 single-nucleotide polymorphism rs4980329 in ALS risk, and a contribution of the APOE-ε2 allele, which was more frequent in ALS patients than in controls. A joint analysis coupling genetic data and sporting activity revealed opposite roles of APOE-ε2 and SIRT3 rs3825075, the former being more frequent in physically active ALS patients and the latter more frequent in physically inactive patients. These findings suggest a contribution to ALS risk of genetic and environmental factors involved in energy metabolism, and stress the importance of a multifactorial analysis for evaluating this risk.
KW - Amyotrophic lateral sclerosis
KW - Apolipoprotein E
KW - Physical activity
KW - PPARGC1A
KW - Sirtuin 3
UR - http://www.scopus.com/inward/record.url?scp=85019248208&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85019248208&partnerID=8YFLogxK
U2 - 10.1266/ggs.16-00023
DO - 10.1266/ggs.16-00023
M3 - Article
C2 - 28239025
AN - SCOPUS:85019248208
VL - 91
SP - 301
EP - 309
JO - Genes and Genetic Systems
JF - Genes and Genetic Systems
SN - 1341-7568
IS - 6
ER -