Evaluation of PINK1 variants in Indian Parkinson's disease patients

Biswas, Arindam; Sadhukhan, Tamal; Majumder, Sayantani; Misra, Amar K.; Das, Shyamal K.; Variation Consortium, Indian Genome; Ray, Kunal; Ray, Jharna

doi:10.1016/j.parkreldis.2009.10.005

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Volume 16, Issue 3 , Pages 167-171, March 2010

Evaluation of PINK1 variants in Indian Parkinson's disease patients☆

Arindam Biswas
- S. N. Pradhan Centre for Neurosciences, University of Calcutta, Kolkata, India
Tamal Sadhukhan
- S. N. Pradhan Centre for Neurosciences, University of Calcutta, Kolkata, India
Sayantani Majumder
- S. N. Pradhan Centre for Neurosciences, University of Calcutta, Kolkata, India
Amar K. Misra
- Movement Disorders Clinic, Bangur Institute of Neurosciences & Psychiatry, Kolkata, India
Shyamal K. Das
- Movement Disorders Clinic, Bangur Institute of Neurosciences & Psychiatry, Kolkata, India
Indian Genome Variation Consortium
- Nodal Laboratory, Institute of Genomics and Integrative Biology, New Delhi, India
Kunal Ray
- Molecular & Human Genetics Division, Indian Institute of Chemical Biology, Kolkata, India
Jharna Ray
- S. N. Pradhan Centre for Neurosciences, University of Calcutta, Kolkata, India
- Corresponding author at: S. N. Pradhan Centre for Neurosciences, University of Calcutta, 35 Ballygunge Circular Road, Kolkata 700 019, India. Tel.: +91 33 2223 2084; fax: +91 33 2223 3260.

Received 25 February 2009; received in revised form 1 September 2009; accepted 12 October 2009.

Abstract

Mutations in PINK1 have been identified in familial and sporadic cases of early onset Parkinson's disease (PD). To determine the contribution of PINK1 variants in Indian PD patients, the gene was screened in 250 patients and 205 ethnically matched controls by polymerase chain reaction, single-stranded conformation polymorphism and DNA sequencing. Two potentially pathogenic variants (Arg246Gln & Arg276Gln) were detected in the heterozygous state in 5 patients; none of the patients carried homozygous or compound heterozygous mutations. In addition, 13 other variants were identified, including a known polymorphism (Ala340Thr), a few synonymous or intronic changes, none of which are likely to be pathogenic. Unlike the Chinese population, the Ala340Thr variant did not show any association with PD in Indian population. Six single nucleotide polymorphisms (SNPs) selected from dbSNP were genotyped in 531 normal, healthy individuals representing different ethnic groups of India. Most of the SNP markers were observed to be highly heterozygous among Indians, which could be used for segregation analysis of PINK1 alleles in familial PD cases.

Keywords: PINK1, Parkinson's disease, SNP, Mutation