Mancuso Michelangelo, Conforti Francesca Luisa, Rocchi Anna, Tessitore Alessandro, Muglia Maria, Tedeschi Gioacchino, Panza Daniela, Monsurrò MariaRosaria, Sola Patrizia, Mandrioli Jessica, Choub Anna, DelCorona Alberto, Manca Maria Laura, Mazzei Rosalucia, Sprovieri Teresa, Filosto Massimiliano, Salviati Alessandro, Valentino Paola, Bono Francesco, Caracciolo Manuela, Simone Isabella Laura, La Bella Vincenzo, Majorana Giovanni, Siciliano Gabriele, Murri Luigi, Quattrone Aldo
Department of Neuroscience, Neurological Clinic, University of Pisa, Via Roma 67, 56126 Pisa, Italy.
Neurosci Lett. 2004 Nov 23;371(2-3):158-62. doi: 10.1016/j.neulet.2004.08.060.
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.
线粒体损伤与肌萎缩侧索硬化症（ALS）的发病机制有关。此外，线粒体特异性多态性先前与其他神经退行性疾病有关，如帕金森病、弗里德赖希共济失调和阿尔茨海默病。为了研究线粒体基因组（mtDNA）内的特定基因多态性是否可作为易感性因素并影响散发性ALS（sALS）的临床表型，我们对222例意大利sALS患者和151例匹配对照进行了预先定义的欧洲mtDNA单倍群基因分型。与携带最常见单倍群H的个体相比，归类为单倍群I的个体患ALS的风险显著降低（优势比0.08，95%置信区间0.04 - 0.4，p < 0.01）。按性别、年龄、疾病发病部位和生存情况对数据集进行进一步分层，未发现显著的关联。我们的研究提供了证据，证明线粒体变异对高加索人患ALS风险的影响。此外，它可能有助于阐明在ALS中可检测到的线粒体功能障碍的机制，并且可能与该疾病治疗策略的制定相关。
