Role of Apolipoprotein E, Cathepsin D, and Brain-Derived Neurotrophic Factor in Parkinson’s Disease: A Study from Eastern India

• Published in: Neuromolecular medicine 2019-09, Vol.21 (3), p.287-294
• Main Authors: Pal, Prosenjit, Sadhukhan, Tamal, Chakraborty, Subhadip, Sadhukhan, Sriparna, Biswas, Arindam, Das, Shyamal K., Ray, Kunal, Ray, Jharna
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age of Onset; Aged; Alleles; Apolipoprotein E; Apolipoproteins; Apolipoproteins E - physiology; Biomedical and Life Sciences; Biomedicine; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - physiology; Case-Control Studies; Cathepsin D; Cathepsin D - physiology; Child; Disease; Environmental factors; Etiology; Female; Gene Frequency; Gene polymorphism; Genotype; Haplotypes; Humans; India - epidemiology; Internal Medicine; Male; Middle Aged; Movement disorders; Neural coding; Neurodegenerative diseases; Neurology; Neurosciences; Original Paper; Parkinson Disease - epidemiology; Parkinson Disease - genetics; Parkinson Disease - metabolism; Parkinson's disease; Pathogenesis; Polymorphism, Single Nucleotide; Population genetics; Promoter Regions, Genetic; Protein Isoforms - genetics; Protein Isoforms - physiology; Single-nucleotide polymorphism; Young Adult
• ISSN: 1535-1084; 1559-1174
• DOI: 10.1007/s12017-019-08548-4

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 ε 2, ε 3, and ε 4 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 ε 3 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.