S. N. Pradhan Centre for Neurosciences, University of Calcutta, Kolkata, West Bengal, India.
Bangur Institute of Neurosciences, Kolkata, West Bengal, India.
Neuromolecular Med. 2019 Sep;21(3):287-294. doi: 10.1007/s12017-019-08548-4. Epub 2019 May 28.
Parkinson's disease (PD) is a progressive neurodegenerative disease with complex etiology. Both genetic and environmental factors play significant role. Apart from candidate genes, some modifier genes have been reported to be associated with the altered risk of PD. Previous studies have identified Apolipoprotein E (APOE), Cathepsin D (CTSD), and Brain-Derived Neurotrophic Factor (BDNF) as key players of neurodegenerative pathways with their variants associated with different neurodegenerative diseases. Hence, this study aims to identify the potential role of these modifier genes in the pathogenesis of PD among Eastern Indian PD patients. A case-control study was performed using 302 clinically diagnosed PD patients and 304 ethnically matched controls. Promoter SNPs of APOE (rs449647, rs405509) and BDNF (rs56164415), and coding SNPs of APOE (rs429358, rs7412 resulting in ε2, ε3, and ε4 alleles), CTSD (rs17571), and BDNF (rs6265) were analyzed by PCR-RFLP and bidirectional sequencing. The effect of rs56164415 on BDNF expression was characterized by Luciferase assay. APOEε4 allele was significantly overrepresented (p value = 0.0003) among PD patients, whereas ε3 allele was predominant in the control population. The promoter haplotype (A-rs449647, G-rs405509) of APOE was preponderant among female PD patients posing risk. No association was found for CTSD polymorphism. The 'T/T' genotype of BDNF rs56164415 was overrepresented (p-value = 0.02) among early onset PD patients. Expression of BDNF for the 'T/T' variant was significantly lower (p-value = 0.012) than the 'C/C' variant, suggesting a possible role in PD pathogenesis. This study suggests that APOE and BDNF may serve as modifier loci among eastern Indian PD patients.
帕金森病（PD）是一种具有复杂病因的进行性神经退行性疾病。遗传和环境因素都起着重要作用。除了候选基因外，一些修饰基因已被报道与 PD 风险的改变有关。先前的研究已经确定载脂蛋白 E（APOE）、组织蛋白酶 D（CTSD）和脑源性神经营养因子（BDNF）为神经退行性途径的关键因子，其变体与不同的神经退行性疾病有关。因此，本研究旨在确定这些修饰基因在印度东部 PD 患者发病机制中的潜在作用。使用 302 例临床诊断为 PD 的患者和 304 名种族匹配的对照进行病例对照研究。通过 PCR-RFLP 和双向测序分析了 APOE（rs449647、rs405509）和 BDNF（rs56164415）的启动子 SNP 以及 APOE（rs429358、rs7412 导致 ε2、ε3 和 ε4 等位基因）、CTSD（rs17571）和 BDNF（rs6265）的编码 SNP。通过荧光素酶测定法对 rs56164415 对 BDNF 表达的影响进行了表征。APOEε4 等位基因在 PD 患者中明显过度表达（p 值=0.0003），而 ε3 等位基因在对照组中占优势。APOE 的启动子单倍型（A-rs449647、G-rs405509）在女性 PD 患者中占优势，具有风险。未发现 CTSD 多态性的关联。BDNF rs56164415 的 'T/T' 基因型在早发性 PD 患者中过度表达（p 值=0.02）。BDNF 对 'T/T' 变体的表达明显低于 'C/C' 变体（p 值=0.012），表明其在 PD 发病机制中可能起作用。本研究表明，APOE 和 BDNF 可能是印度东部 PD 患者的修饰基因座。
