title: Could mitochondrial haplogroups play a role in sporadic amyotrophic lateral sclerosis?
abstract: Mitochondrial impairment has been implicated in the pathogenesis of the amyotrophic lateral sclerosis (ALS). Furthermore, mitochondrial-specific polymorphisms were previously related to other neurodegenerative diseases, such as Parkinson, Friedreich and Alzheimer disease. To investigate if specific genetic polymorphisms within the mitochondrial genome (mtDNA) could act as susceptibility factors and contribute to the clinical expression of sporadic ALS (sALS), we have genotyped predefined European mtDNA haplogroups in 222 Italian patients with sALS and 151 matched controls. Individuals classified as haplogroup I demonstrated a significant decrease in risk of ALS versus individuals carrying the most common haplogroup, H (odds ratio 0.08, 95% confidence interval 0.04-0.4, p < 0.01). Further stratification of the dataset by sex, age and site of onset of disease and survival failed to reach significance for association. Our study provides evidence of the contribution of mitochondrial variation to the risk of ALS development in Caucasians. Further it may help elucidate the mechanism of the mitochondrial dysfunction detectable in ALS, and may be of relevance in development of strategies for the treatment of this disease.
authors.affiliation: Department of Neuroscience, Neurological Clinic, University of Pisa, Via Roma 67, 56126 Pisa, Italy. mmancuso@inwind.it
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Mancuso
authors.forename: Francesca Luisa
authors.initials: FL
authors.lastname: Conforti
authors.forename: Anna
authors.initials: A
authors.lastname: Rocchi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Tessitore
authors.forename: Maria
authors.initials: M
authors.lastname: Muglia
authors.forename: Gioacchino
authors.initials: G
authors.lastname: Tedeschi
authors.forename: Daniela
authors.initials: D
authors.lastname: Panza
authors.forename: MariaRosaria
authors.initials: M
authors.lastname: Monsurrò
authors.forename: Patrizia
authors.initials: P
authors.lastname: Sola
authors.forename: Jessica
authors.initials: J
authors.lastname: Mandrioli
authors.forename: Anna
authors.initials: A
authors.lastname: Choub
authors.forename: Alberto
authors.initials: A
authors.lastname: DelCorona
authors.forename: Maria Laura
authors.initials: ML
authors.lastname: Manca
authors.forename: Rosalucia
authors.initials: R
authors.lastname: Mazzei
authors.forename: Teresa
authors.initials: T
authors.lastname: Sprovieri
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Filosto
authors.forename: Alessandro
authors.initials: A
authors.lastname: Salviati
authors.forename: Paola
authors.initials: P
authors.lastname: Valentino
authors.forename: Francesco
authors.initials: F
authors.lastname: Bono
authors.forename: Manuela
authors.initials: M
authors.lastname: Caracciolo
authors.forename: Isabella Laura
authors.initials: IL
authors.lastname: Simone
authors.forename: Vincenzo
authors.initials: V
authors.lastname: La Bella
authors.forename: Giovanni
authors.initials: G
authors.lastname: Majorana
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siciliano
authors.forename: Luigi
authors.initials: L
authors.lastname: Murri
authors.forename: Aldo
authors.initials: A
authors.lastname: Quattrone
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics*; D015331:Cohort Studies; D016001:Confidence Intervals; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial