Could mitochondrial haplogroups play a role in sporadic amyotrophic lateral sclerosis?
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.
Mancuso
Michelangelo
M
Department of Neuroscience, Neurological Clinic, University of Pisa, Via Roma 67, 56126 Pisa, Italy. mmancuso@inwind.it
Conforti
Francesca Luisa
FL
Rocchi
Anna
A
Tessitore
Alessandro
A
Muglia
Maria
M
Tedeschi
Gioacchino
G
Panza
Daniela
D
Monsurrò
MariaRosaria
M
Sola
Patrizia
P
Mandrioli
Jessica
J
Choub
Anna
A
DelCorona
Alberto
A
Manca
Maria Laura
ML
Mazzei
Rosalucia
R
Sprovieri
Teresa
T
Filosto
Massimiliano
M
Salviati
Alessandro
A
Valentino
Paola
P
Bono
Francesco
F
Caracciolo
Manuela
M
Simone
Isabella Laura
IL
La Bella
Vincenzo
V
Majorana
Giovanni
G
Siciliano
Gabriele
G
Murri
Luigi
L
Quattrone
Aldo
A
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
D004272:DNA, Mitochondrial