Yonsei Med J.  2018 Aug;59(6):787-792. 10.3349/ymj.2018.59.6.787.

Effect of rs3910105 in the Synuclein Gene on Dopamine Transporter Availability in Healthy Subjects

• Seo Y
• Pak K
• Nam HY
• Seok JW
• Lee MJ
• Kim EJ
• Lee JM
• Kim SJ
• Kim IJ

• KMID: 2415538
• DOI: http://doi.org/10.3349/ymj.2018.59.6.787

Abstract

PURPOSE
The present study investigated associations between dopamine transporter (DAT) availability and α-synuclein levels in cerebrospinal fluid, as well as synuclein gene (SNCA) transcripts, and the effect of single nucleotide polymorphism of SNCA on DAT availability in healthy subjects.
MATERIALS AND METHODS
The study population comprised healthy controls who underwent 123I-FP-CIT 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 3"²UTR region (SNCA-3UTR-1, SNCA-3UTR-2), transcripts that skip exon 5 (SNCA-E4E6), and the rare short transcript isoforms that comprise exons 1-4 (SNCA-007).
RESULTS
In total, 123 healthy subjects (male 75, female 48) were included in this study. DAT availability in the caudate nucleus (p=0.0661) and putamen (p=0.0739) tended to differ according to rs3910105 genotype. In post-hoc analysis, DAT 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 (p=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.

Keyword

Dopamine plasma membrane transport proteins; synucleins; genotype; single-photon emission computed tomography; biomarkers

MeSH Terms

Biomarkers
Caudate Nucleus
Cerebrospinal Fluid
Dopamine Plasma Membrane Transport Proteins*
Dopamine*
Exons
Female
Genotype
Healthy Volunteers*
Humans
Mass Screening
Polymorphism, Single Nucleotide
Protein Isoforms
Putamen
Synucleins*
Tomography, Emission-Computed
Biomarkers
Dopamine
Dopamine Plasma Membrane Transport Proteins
Protein Isoforms
Synucleins

Figure

• 

  Fig. 1 Post-hoc analysis of dopamine transporter availability in the caudate nucleus (p=0.0597) and putamen (p=0.0317) according to genotypes of rs3910105.

• 

  Fig. 2 Correlation between dopamine transporter availability of putamen in subjects with CT genotype of rs3910105 and (A) SNCA-E3E4 (p=0.037, rho=−0.277) and (B) SNCA-E4E6 (p=0.042, rho=−0.270).

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