Ai San-xi, Xu Qian, Hu Ya-cen, Song Cheng-yuan, Guo Ji-feng, Shen Lu, Wang Chun-rong, Yu Ri-li, Yan Xin-xiang, Tang Bei-sha
Department of Neurology, Xiangya Hospital, Central South University, Changsha, China.
Department of Geriatric Neurology, Xiangya Hospital, Central South University, Changsha, China.
J Neurol Sci. 2014 Feb 15;337(1-2):123-8. doi: 10.1016/j.jns.2013.11.033. Epub 2013 Dec 1.
SNCA is a pathogenic gene identified in rare familial PD, and over-expression of SNCA was suggested in the pathogenesis of familial and sporadic PD. Rep1 polymorphism of SNCA was associated with susceptibility to sporadic PD and SNCA expression in intro and in vivo. Hypomethylation in SNCA intron-1 was associated with increased SNCA expression and was observed in postmortem brains of patients with sporadic PD. We studied the methylation status of SNCA intron-1, SNCA mRNA levels and Rep1 genotypes in PBMCs of 100 sporadic PD patients and 95 controls and explored the relationship between DNA methylation, mRNA expression and Rep1 genotypes. Hypomethylation of SNCA intron-1 was detected in PBMCs of PD patients, and DNA methylation levels were associated with Rep1 polymorphism. The shorter allele was associated with higher level of SNCA intron-1 methylation, and genotypes carrying the shorter allele showed significantly higher methylation level of SNCA intron-1 than genotypes carrying the longer allele. However, SNCA mRNA levels were not associated with disease status, Rep1 polymorphism or DNA methylation of SNCA intron-1 in our study.
α-突触核蛋白（SNCA）是在罕见家族性帕金森病（PD）中鉴定出的致病基因，并且在家族性和散发性PD的发病机制中提示存在SNCA过表达。SNCA的Rep1多态性与散发性PD的易感性以及体内外SNCA表达相关。SNCA内含子1的低甲基化与SNCA表达增加相关，并且在散发性PD患者的尸检大脑中观察到。我们研究了100例散发性PD患者和95例对照外周血单核细胞（PBMC）中SNCA内含子1的甲基化状态、SNCA mRNA水平和Rep1基因型，并探讨了DNA甲基化、mRNA表达和Rep1基因型之间的关系。在PD患者的PBMC中检测到SNCA内含子1的低甲基化，并且DNA甲基化水平与Rep1多态性相关。较短的等位基因与SNCA内含子1较高的甲基化水平相关，携带较短等位基因的基因型显示SNCA内含子1的甲基化水平显著高于携带较长等位基因的基因型。然而，在我们的研究中，SNCA mRNA水平与疾病状态、Rep1多态性或SNCA内含子1的DNA甲基化无关。
