Affiliations: S. N. Pradhan Centre for Neurosciences, University of
Calcutta, Kolkata, India | Molecular and Human Genetics Division, CSIR-Indian
Institute of Chemical Biology, Kolkata, India | Genomics and Molecular Medicine, CSIR-Institute of
Genomics and Integrative Biology, Delhi | Movement Disorders Clinic, Bangur Institute of
Neurosciences, Kolkata, India
Note: [] Dr. Kunal Ray, Molecular & Human Genetics Division,
CSIR-Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata
– 700 032, India. Tel.: +91 33 2483 1984; Fax: +91 33 2473 5197; E-mail:
[email protected], [email protected]; Prof. Jharna Ray, 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;
E-mail: [email protected], [email protected]
Abstract: Leucine rich repeat kinase 2 (LRRK2) gene defects cause Parkinson's
disease (PD). Recently, LRRK2 has also been shown by genome wide association
(GWA) studies to be a susceptibility gene for the disease. In India mutations
in LRRK2 is a rare cause of PD. We, therefore, genotyped 64 SNPs across LRRK2
in 161 control samples and finally studied 6 haplotype tagging SNPs for
association-based study on 300 cases and 446 ethnically matched controls to
explore the potential role of LRRK2 as a susceptibility gene in PD for East
Indians. We did not find any significant allele/ genotype or haplotype
associations with PD suggesting that common genetic variants within LRRK2 play
limited role in modulating PD among East Indians. In addition, we also screened
for the common mutations (viz. p.R1441C, p.R1441G, p.R1441H, p.Y1699C,
p.G2019S), and a risk variant common among Asians (p.G2385R) but did not
observe any of the above mentioned variants in our cohort. Our study,
therefore, strongly suggests that LRRK2 has minimal role as a candidate and
susceptibility gene in PD pathogenesis among East Indians.
Keywords: Haplotype, LRRK2, mutation, Parkinson's disease, SNP
