Journal
YONSEI MEDICAL JOURNAL
Volume 59, Issue 6, Pages 787-792Publisher
YONSEI UNIV COLL MEDICINE
DOI: 10.3349/ymj.2018.59.6.787
Keywords
Dopamine plasma membrane transport proteins; synucleins; genotype; single-photon emission computed tomography; biomarkers
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Funding
- Michael J. Fox Foundation for Parkinson's Research
- abbVie
- Avid
- Biogen
- Bristol-Myers Squibb
- COVANCE
- GE Healthcare
- Genentech
- GlaxoSmithKline
- Lundbeck
- Lilly
- Merck
- MesoScaleDiscovery
- Pfizer
- Piramal
- Roche
- Sanofi Genzyme
- Servier
- TEVA
- UCB
- Basic Science Research Program through the National Research Foundation of Korea (NRF) [2017R1D1A1B03029352/2017R1D1A1B03033235/201 8R1C1B5030638]
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Purpose: The present study investigated associations between dopamine transporter (DAT) availability and alpha-synudein levels in cerebrospinal fluid, as well as synuclein gene (SNCA) transcripts, and the effect of single nucleotide polymorphism of SNCA on mu availability in healthy subjects. Materials and Methods: The study population comprised healthy controls who underwent I-123-Fp-crr single-photon emission computed tomography screening. Five SNCA probes were used to target the boundaries of exon 3 and exon 4 (SNCA-E3E4), transcripts with a long TUTR region (SNCA-3'UTR-1, SNCA-3UTR-2), transcripts that skip exon 5 (SNCA-E4E6), and the rare short transcript isoforms that comprise exon 1-4 (SNCA-007). Results: In total, 123 healthy subjects (male 75, female 48) were included in this study. DM availability in the caudate nucleus (p=0.0661) and putamen (p=0.0739) tended to differ according to rs3910105 genotype. In post-hoc analysis, DM availability in the putamen was lower in subjects of TT genotype than those of CC/CT (p=0.0317). DAT availability in the caudate nucleus also showed a trend similar to that in the putamen (p=0.0597). Subjects of CT genotype with rs3910105 showed negative correlations with DAT availability in the putamen with SNCA-E3E4 (p=0.037, rho=-0.277), and SNCA-E4E6 ( 0.042, rho=-0.270), but not those of CC/TT genotypes. Conclusion: This is the first study to investigate the association of rs3910105 in SNCA with DAT availability. rs3910105 had an effect on DAT availability, and the correlation between DAT availability and SNCA transcripts were significant in CT genotypes of rs3910105.
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