Evaluation of PARKIN gene variants in West Bengal Parkinson's disease patients

• Published in: Journal of human genetics Vol. 60; no. 9; pp. 485 - 492
• Main Authors: Sanyal, Jaya, Jana, Arpita, Ghosh, Epsita, Banerjee, Tapas K, Chakraborty, Durga P, Rao, Vadlamudi R
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01-09-2015
• Subjects: Adult; Aged; Aged, 80 and over; Case-Control Studies; Cerebrospinal fluid; DNA sequencing; Exons; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease - ethnology; Humans; India - epidemiology; Linkage disequilibrium; Male; Middle Aged; Movement disorders; Mutation; Neurodegenerative diseases; Parkin protein; Parkinson Disease - epidemiology; Parkinson Disease - genetics; Parkinson's disease; Patients; Polymerase chain reaction; Polymorphism, Single Nucleotide; Risk factors; Single-nucleotide polymorphism; Splice junctions; Ubiquitin-Protein Ligases - genetics; West Bengal India; India
• ISSN: 1434-5161; 1435-232X
• DOI: 10.1038/jhg.2015.49

Little information is available regarding the molecular pathogenesis of Parkinson's disease (PD) among the Bengalee population in West Bengal, India. This study was undertaken to determine the contribution of Parkin variants in well-defined ethnically identical Bengalee population of India and further to describe the clinical spectrum associated with these mutations. A total of 150 unrelated PD patients and 150 controls were recruited for the study. The entire cohort was screened for mutations in all the 12 exons of the gene along with flanking splice junctions by polymerase chain reaction and DNA sequencing. Eleven nucleotide variants including two novel changes were detected. Cerebrospinal fluid (CSF) parkin protein expression of the novel mutation, Val186Ile (found in heterozygous condition in one patient only) was almost 2.7 folds lower than the controls and other PD patients. Molecular characterization of polymorphisms Ser167Asn and Val380Leu depicted that homozygous Ser167 and Val380 are significantly associated with the disease. We did not find any linkage disequilibrium among the SNPs, the low r(2) for every pair of single-nucleotide polymorphisms (SNPs) indicated that these SNPs cannot be tagged by each other. Another novel intronic change, IVS8+48C>T was present in almost equally in PD patients and controls. Among the ethnically defined Bengalee population of West Bengal, occurrence of Parkin mutation is 4% (6/150) of the PD patient pool supported with decreased folds of expression of CSF PARKIN protein. Parkin polymorphisms, Ser167 and Val380 are risk factors for the progression of the disease, and their frequency is greatly influenced by ethnic origin.