title: The role of single-nucleotide variants of the energy metabolism-linked genes SIRT3, PPARGC1A and APOE in amyotrophic lateral sclerosis risk.
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.
authors.affiliation: Laboratory of Biology of Neurodegenerative Disorders, Department of Neuroscience, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri.
authors.forename: Diego
authors.initials: D
authors.lastname: Albani
authors.affiliation: Laboratory of Neurological Diseases, Department of Neuroscience, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Pupillo
authors.affiliation: Laboratory of Neurological Diseases, Department of Neuroscience, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri.
authors.forename: Elisa
authors.initials: E
authors.lastname: Bianchi
authors.affiliation: Laboratory of Biology of Neurodegenerative Disorders, Department of Neuroscience, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri.
authors.forename: Armando
authors.initials: A
authors.lastname: Chierchia
authors.affiliation: Laboratory of Biology of Neurodegenerative Disorders, Department of Neuroscience, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri.
authors.forename: Rosalba
authors.initials: R
authors.lastname: Martines
authors.affiliation: Laboratory of Biology of Neurodegenerative Disorders, Department of Neuroscience, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri.
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Forloni
authors.affiliation: Laboratory of Neurological Diseases, Department of Neuroscience, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri.
authors.forename: Ettore
authors.initials: E
authors.lastname: Beghi
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D016022:Case-Control Studies; D015444:Exercise; D005260:Female; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D056566:Sirtuin 3 / Q000235:genetics*
chemical_list: C000612345:ApoE protein, human; D001057:Apolipoproteins E; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C466093:SIRT3 protein, human; D056566:Sirtuin 3
keywords: PPARGC1A; amyotrophic lateral sclerosis; apolipoprotein E; physical activity; sirtuin 3