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, mitochondrialspecificpolymorphisms 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 contributeto the clinical expression of sporadic ALS (sALS), we have genotyped predefined European mtDNA haplogroups in 222 Italian patients withsALS and 151 matched controls. Individuals classified as haplogroup I demonstrated a significant decrease in risk of ALS versus individualscarrying the most common haplogroup, H (odds ratio 0.08, 95% confidence interval 0.04-0.4, p < 0.01). Further stratification of the datasetby 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 mayhelp elucidate the mechanism of the mitochondrial dysfunction detectable in ALS, and may be of relevance in development of strategies forthe treatment of this disease.