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.

中文翻译：

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载脂蛋白E，组织蛋白酶D和脑源性神经营养因子在帕金森氏病中的作用：来自印度东部的一项研究。

帕金森氏病（PD）是一种病因复杂的进行性神经退行性疾病。遗传因素和环境因素均起着重要作用。除了候选基因，据报道一些修饰基因与PD风险的改变有关。先前的研究已经确定了载脂蛋白E（APOE），组织蛋白酶D（CTSD）和脑源性神经营养因子（BDNF））作为神经变性途径的关键参与者，其变体与不同的神经变性疾病有关。因此，本研究旨在确定这些修饰基因在印度东部PD患者中PD发病机理中的潜在作用。病例对照研究使用了302名经过临床诊断的PD患者和304名种族匹配的对照。的启动子的SNP APOE（rs449647，rs405509）和BDNF（rs56164415），及编码SNP APOE（rs429358，导致rs7412 ε 2，ε 3和ε 4个等位基因），CTSD（rs17571）和BDNF（rs6265）通过PCR-RFLP和双向测序进行分析。通过荧光素酶测定来表征rs56164415对BDNF表达的影响。在PD患者中，APOEε4等位基因明显过多（p值= 0.0003），而在对照组中ε3等位基因占主导。APOE的启动子单倍型（A-rs449647，G-rs405509）在构成风险的女性PD患者中占优势。没有发现CTSD多态性。在早期发作的PD患者中，BDNF rs56164415的“ T / T”基因型过高（p值= 0.02）。'T / T'变体的BDNF表达显着降低（p-值= 0.012），而不是“ C / C”变体，表明在PD发病机理中可能发挥作用。这项研究表明，APOE和BDNF可能是印度东部PD患者中的修饰位点。