Abstract
The alpha-synuclein–caveolin 1 axis is suggested to be of role in the pathogenesis of Parkinson’s disease in cell line models. The objective of this study was to analyze the homozygous haplotype compartment of the human caveolin 1 gene upstream purine complex in patients afflicted with Parkinson’s disease. This complex was screened in patients with Parkinson’s disease (n = 141) and compared with a group of controls (n = 760) using polymerase chain reaction and sequencing. The expression activity of the homozygous haplotypes was then examined using luciferase Dual-Glo system in human neuronal cell line, LAN-5. Six haplotypes were found to be homozygous in the patients, and not in the control pool (Fisher exact p < 1 × 10−6). Three of those haplotypes were specific to Parkinson’s disease (Fisher exact p < 0.002), and the remaining three overlapped with homozygous haplotypes in Alzheimer’s disease and multiple sclerosis (Fisher exact p < 0.002). The disease haplotypes contained motif lengths that were nonexistent in the control homozygous haplotype pool and significantly increased gene expression (p < 9 × 10—6). We conclude that skew in the caveolin 1 purine complex homozygous haplotype compartment and an additive effect of those haplotypes may be linked with Parkinson’s disease.
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Acknowledgments
This study was supported by the University of Social Welfare and Rehabilitation Sciences, Tehran, Iran, grant no. 64032 to M. Ohadi.
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ESM Fig. S1
Novel homozygous haplotypes observed in PD patients, only (JPEG 95 kb)
ESM Fig. S2
Overlapping homozygous haplotypes between PD and other neurodegenerative disorders: AD and MS (JPEG 97 kb)
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Darvish, H., Heidari, A., Hosseinkhani, S. et al. Biased Homozygous Haplotypes Across the Human Caveolin 1 Upstream Purine Complex in Parkinson’s Disease. J Mol Neurosci 51, 389–393 (2013). https://doi.org/10.1007/s12031-013-0021-9
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DOI: https://doi.org/10.1007/s12031-013-0021-9