促红细胞生成素基因是肌萎缩侧索硬化症的修饰因子吗？

Is erythropoietin gene a modifier factor in amyotrophic lateral sclerosis?

作者信息

Ghezzi Serena, Del Bo Roberto, Scarlato Marina, Nardini Martina, Carlesi Cecilia, Prelle Alessandro, Corti Stefania, Mancuso Michelangelo, Briani Chiara, Siciliano Gabriele, Murri Luigi, Bresolin Nereo, Comi Giacomo Pietro

机构信息

Dino Ferrari Centre, Department of Neurological Sciences, University of Milan, IRCCS Foundation Ospedale Maggiore Policlinico Mangiagalli and Regina Elena, Padiglione Ponti. Via F. Sforza 35, 20122 Milano, Italy.

出版信息

Neurobiol Aging. 2009 May;30(5):842-4. doi: 10.1016/j.neurobiolaging.2007.08.008. Epub 2007 Sep 20.

DOI:10.1016/j.neurobiolaging.2007.08.008

PMID:17888545

Abstract

To investigate the role of erythropoietin (EPO) as genetic determinant in the susceptibility to sporadic amyotrophic lateral sclerosis (SALS). We sequenced a 259-bp region spanning the 3'hypoxia-responsive element of the EPO gene in 222 Italian SALS patients and 204 healthy subjects, matched for age and ethnic origin. No potentially causative variation was detected in SALS subjects; in addition, two polymorphic variants (namely C3434T and G3544T) showed the same genotype and haplotype frequencies in patients and controls. Conversely, a weak but significant association between G3544T and age of disease onset was observed (p=0.04). Overall, our data argue against the hypothesis of EPO as a genetic risk factor for motor neuron dysfunction, at least in Italian population. However, further studies on larger cohort of patients are needed to confirm the evidence of EPO gene as modifier factor.

摘要

为研究促红细胞生成素（EPO）作为遗传决定因素在散发性肌萎缩侧索硬化症（SALS）易感性中的作用。我们对222例意大利SALS患者和204名年龄及种族匹配的健康对照者的EPO基因3'缺氧反应元件所在的一段259 bp区域进行了测序。在SALS患者中未检测到潜在的致病变异；此外，两个多态性变异（即C3434T和G3544T）在患者和对照中显示出相同的基因型和单倍型频率。相反，观察到G3544T与疾病发病年龄之间存在微弱但显著的关联（p = 0.04）。总体而言，我们的数据至少在意大利人群中反对EPO作为运动神经元功能障碍遗传风险因素的假说。然而，需要对更大规模的患者队列进行进一步研究，以确认EPO基因作为修饰因子的证据。