Department of Neurology, National Key Clinical Department and Key Discipline of Neurology The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Guangxi, China.
J Gene Med. 2017 Nov;19(11):360-365. doi: 10.1002/jgm.2991. Epub 2017 Nov 19.
Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. Epigenetic modifications, specifically DNA methylation, have been implicated in the development of this disease. Genetic variants of DNA methyltransferase 3b (DNMT3b), one of the most important DNA methyltransferases, were shown to be associated with PD in a Brazilian population. However, it is unclear whether genetic variants of DNMT3b increase the risk of PD in the Chinese Han people. The present study aimed to investigate the association of the DNMT3b variants rs2424913, rs998382 and rs2424932 with PD in a Chinese Han population.
We studied 487 Chinese Han patients with sporadic PD and 485 healthy age-, sex- and ethnicity-matched controls. DNA was extracted from peripheral blood leukocytes and the individual genotypes were determined using the SNaPshot method.
We found that the rs2424932 and rs998382 variants were significantly associated with an increased risk of PD compared to the controls [rs2424932: odds ratio (OR) = 1.632, 95% confidence interval (CI) = 1.108-2.406, p = 0.013; rs998382: OR = 1.612, 95% CI = 1.103-2.382, p = 0.014]. Subgroup analysis suggested that female patients carrying the rs2424932 or rs998382 variants were more likely to develop PD than female controls (rs2424932: OR = 3.863, 95% CI = 2.004-7.445, p < 0.001; rs998382: OR = 3.679, 95% CI = 1.943-6.964, p < 0.001). Haplotype analysis indicated that the three variants comprised one block and that the T -C -A haplotype was correlated with an increased risk of PD (p = 0.0046), especially for Chinese Han females (p < 0.0001).
The results of the present study strongly suggest that DNMT3b variants are associated with PD in the Chinese Han people, especially females.
帕金森病（PD）是全球第二常见的神经退行性疾病。表观遗传修饰，特别是 DNA 甲基化，与这种疾病的发生有关。DNA 甲基转移酶 3b（DNMT3b）的遗传变异体是最重要的 DNA 甲基转移酶之一，在巴西人群中与 PD 相关。然而，DNMT3b 遗传变异体是否会增加中国汉族人群患 PD 的风险尚不清楚。本研究旨在探讨中国汉族人群中 DNMT3b 变异体 rs2424913、rs998382 和 rs2424932 与 PD 的相关性。
我们研究了 487 例中国汉族散发性 PD 患者和 485 例年龄、性别和种族匹配的健康对照者。从外周血白细胞中提取 DNA，并使用 SNaPshot 方法确定个体基因型。
我们发现 rs2424932 和 rs998382 变异体与 PD 风险增加显著相关，与对照组相比 [rs2424932：比值比（OR）=1.632，95%置信区间（CI）=1.108-2.406，p=0.013；rs998382：OR=1.612，95%CI=1.103-2.382，p=0.014]。亚组分析表明，携带 rs2424932 或 rs998382 变异体的女性患者比女性对照组更易患 PD（rs2424932：OR=3.863，95%CI=2.004-7.445，p<0.001；rs998382：OR=3.679，95%CI=1.943-6.964，p<0.001）。单体型分析表明，这三个变异体构成一个块，T-C-A 单体型与 PD 风险增加相关（p=0.0046），特别是对中国汉族女性（p<0.0001）。
本研究结果强烈提示，DNMT3b 变异体与中国汉族人群 PD 相关，特别是女性。
