Seo Youngduk, Pak Kyoungjune, Nam Hyun Yeol, Seok Ju Won, Lee Myung Jun, Kim Eun Joo, Lee Jae Meen, Kim Seong Jang, Kim In Joo
Department of Nuclear Medicine, Busan Seongso Hospital, Busan, Korea.
Department of Nuclear Medicine and Biomedical Research Institute, Pusan National University Hospital, Busan, Korea.
Yonsei Med J. 2018 Aug;59(6):787-792. doi: 10.3349/ymj.2018.59.6.787.
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.
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'UTR 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).
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.
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.
本研究调查了健康受试者中多巴胺转运体（DAT）可用性与脑脊液中α-突触核蛋白水平、突触核蛋白基因（SNCA）转录本之间的关联，以及SNCA单核苷酸多态性对DAT可用性的影响。
研究人群包括接受¹²³I-FP-CIT单光子发射计算机断层扫描筛查的健康对照者。使用五个SNCA探针靶向第3外显子和第4外显子的边界（SNCA-E3E4）、具有长3'非翻译区的转录本（SNCA-3UTR-1、SNCA-3UTR-2）、跳过第5外显子的转录本（SNCA-E4E6）以及包含第1-4外显子的罕见短转录本异构体（SNCA-007）。
本研究共纳入123名健康受试者（男性75名，女性48名）。尾状核（p = 0.0661）和壳核（p = 0.0739）中的DAT可用性根据rs3910105基因型有差异趋势。在事后分析中，TT基因型受试者壳核中的DAT可用性低于CC/CT基因型受试者（p = 0.0317）。尾状核中的DAT可用性也显示出与壳核中相似的趋势（p = 0.0597）。rs3910105的CT基因型受试者中，壳核中的DAT可用性与SNCA-E3E4（p = 0.037，rho = -0.277）和SNCA-E4E6（p = 0.042，rho = -0.270）呈负相关，但CC/TT基因型受试者则不然。
这是第一项研究SNCA中rs3910105与DAT可用性之间关联的研究。rs3910105对DAT可用性有影响，且在rs3910105的CT基因型中，DAT可用性与SNCA转录本之间的相关性显著。
