Gusdon Aaron M, Fang Fang, Chen Jing, Mathews Clayton E, Li Wang, Chu Charleen T, Ding Jian-Qing, Chen Sheng-di
Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, No. 197, Rui Jin Er Road, Shanghai 200025, China; Department of Pathology, Division of Neuropathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Department of Neurology, Weill Cornell Medical College, New York, NY 10065, USA.
Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, No. 197, Rui Jin Er Road, Shanghai 200025, China.
Neurosci Lett. 2015 Feb 5;587:98-101. doi: 10.1016/j.neulet.2014.12.005. Epub 2014 Dec 12.
Mitochondria play an important role in the etiology of Parkinson's disease (PD). While mutations in the mitochondrial DNA (mtDNA) have been shown to accumulate in PD, no specific mtDNA polymorphisms have been associated with susceptibility or resistance to PD. A cytosine to adenine transversion at base pair 5178 in the mtDNA has been associated with increased longevity and resistance against a number of age related disorders and has been shown to decrease mitochondrial reactive oxygen species (ROS) production. We sought to determine whether 5178A is associated with resistance against PD in a Han Chinese population. To assess its association with PD, we genotyped 484 idiopathic PD patients and 710 control individuals for 5178C/A. Genotyping was performed using restriction fragment length polymorphism (RFLP) analysis. There was no significant association between 5178A and PD (P=0.308) when analyzing the entire population. However, sub-group analysis revealed that in males the frequency of 5178A was significantly lower in PD patients (27.7% in controls vs 20.0% in PD patients, P=0.027). Stratification of the population by age showed that this trend held across age groups but only reached statistical significance in males aged 60-70 (29.1% in controls vs 14.05 in PD patients, P=0.011). In conclusion, we demonstrated that the frequency of 5178A was significantly decreased in male PD patients in a Han Chinese population. This polymorphism may be associated with resistance against the development of PD when in combination with loci on the Y chromosome.
线粒体在帕金森病（PD）的病因学中起着重要作用。虽然已证实在PD中线粒体DNA（mtDNA）的突变会累积，但尚无特定的mtDNA多态性与PD的易感性或抗性相关。mtDNA中第5178个碱基对处的胞嘧啶到腺嘌呤的颠换与寿命延长以及对多种与年龄相关疾病的抗性有关，并且已显示可减少线粒体活性氧（ROS）的产生。我们试图确定5178A是否与中国汉族人群对PD的抗性有关。为了评估其与PD的关联，我们对484例特发性PD患者和710例对照个体进行了5178C/A基因分型。使用限制性片段长度多态性（RFLP）分析进行基因分型。在分析整个人群时，5178A与PD之间没有显著关联（P=0.308）。然而，亚组分析显示，在男性中，PD患者中5178A的频率显著较低（对照组为27.7%，PD患者为20.0%，P=0.027）。按年龄对人群进行分层显示，这种趋势在各年龄组中均存在，但仅在60-70岁的男性中达到统计学显著性（对照组为29.1%，PD患者为14.05%，P=0.011）。总之，我们证明在中国汉族人群中，男性PD患者中5178A的频率显著降低。这种多态性可能与Y染色体上的基因座结合时对PD发展的抗性有关。
