Effect of rs3910105 in the Synuclein Gene on Dopamine Transporter Availability in Healthy Subjects
3
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Purpose: The present study investigated associations between dopamine transporter (DAT) availability and α-synuclein levels incerebrospinal fluid, as well as synuclein gene (SNCA) transcripts, and the effect of single nucleotide polymorphism of SNCA onDAT availability in healthy subjects. Materials and Methods: The study population comprised healthy controls who underwent 123I-FP-CIT single-photon emissioncomputed tomography screening. Five SNCA probes were used to target the boundaries of exon 3 and exon 4 (SNCA-E3E4), transcriptswith a long 3’UTR region (SNCA-3UTR-1, SNCA-3UTR-2), transcripts that skip exon 5 (SNCA-E4E6), and the rare shorttranscript 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 inthe putamen was lower in subjects of TT genotype than those of CC/CT (p=0.0317). DAT availability in the caudate nucleus alsoshowed a trend similar to that in the putamen (p=0.0597). Subjects of CT genotype with rs3910105 showed negative correlationswith DAT availability in the putamen with SNCA-E3E4 (p=0.037, rho=-0.277), and SNCA-E4E6 (p=0.042, rho=-0.270), but notthose of CC/TT genotypes. Conclusion: This is the first study to investigate the association of rs3910105 in SNCA with DAT availability. rs3910105 had an effecton DAT availability, and the correlation between DAT availability and SNCA transcripts were significant in CT genotypes ofrs3910105.
Abstract
Purpose: The present study investigated associations between dopamine transporter (DAT) availability and α-synuclein levels incerebrospinal fluid, as well as synuclein gene (SNCA) transcripts, and the effect of single nucleotide polymorphism of SNCA onDAT availability in healthy subjects. Materials and Methods: The study population comprised healthy controls who underwent 123I-FP-CIT single-photon emissioncomputed tomography screening. Five SNCA probes were used to target the boundaries of exon 3 and exon 4 (SNCA-E3E4), transcriptswith a long 3’UTR region (SNCA-3UTR-1, SNCA-3UTR-2), transcripts that skip exon 5 (SNCA-E4E6), and the rare shorttranscript 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 inthe putamen was lower in subjects of TT genotype than those of CC/CT (p=0.0317). DAT availability in the caudate nucleus alsoshowed a trend similar to that in the putamen (p=0.0597). Subjects of CT genotype with rs3910105 showed negative correlationswith DAT availability in the putamen with SNCA-E3E4 (p=0.037, rho=-0.277), and SNCA-E4E6 (p=0.042, rho=-0.270), but notthose of CC/TT genotypes. Conclusion: This is the first study to investigate the association of rs3910105 in SNCA with DAT availability. rs3910105 had an effecton DAT availability, and the correlation between DAT availability and SNCA transcripts were significant in CT genotypes ofrs3910105.
참고문헌 (34)
- Spillantini MG, "alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with lewy bodies", Proc Natl Acad Sci U S A, 95, pp.6469~6473 (1998)[DOI]
- Politis M, "Neuroimaging in Parkinson disease: from research setting to clinical practice", Nat Rev Neurol, 10, pp.708~722 (2014)[DOI]
- Park E, "A new era of clinical dopamine transporter imaging using 123I-FP-CIT", J Nucl Med Technol, 40, pp.222~228 (2012)[DOI]
- Booth TC, "The role of functional dopamine-transporter SPECT imaging in parkinsonian syndromes, part 1", AJNR Am J Neuroradiol, 36, pp.229~235 (2015)[DOI]
- Marshall V, "Role of dopamine transporter imaging in routine clinical practice", Mov Disord, 18, pp.1415~1423 (2003)[DOI]
- Zipursky RB, "PET and SPECT imaging in psychiatric disorders", Can J Psychiatry, 52, pp.146~157 (2007)[DOI]
- Thomas AJ, "Autopsy validation of 123I-FP-CIT dopaminergic neuroimaging for the diagnosis of DLB", Neurology, 88, pp.276~283 (2017)[DOI]
- FP-CIT in the thalamus and pons: gender and age dependencies assessed in a European multicentre database of healthy controls, "Eur J Nucl Med Mol Imaging", 2014, 1938~1946, 10.1007[DOI]
- Stefanis L, "<TEX>${\alpha}$<", TEX>-Synuclein in Parkinson's disease, 2012, pp.2, a009399~
- Beyer K, "Alpha-synuclein structure, posttranslational modification and alternative splicing as aggregation enhancers", Acta Neuropathol, 112, pp.237~251 (2006)[DOI]
- Bisaglia M, "Structural insights on physiological functions and pathological effects of alpha-synuclein", FASEB J, 23, pp.329~340 (2009)[DOI]
- Sidhu A, "alpha-Synuclein regulation of the dopaminergic transporter: a possible role in the pathogenesis of Parkinson's disease", FEBS Lett, 565, pp.1~5 (2004)[DOI]
- Perez RG, "A role for alpha-synuclein in the regulation of dopamine biosynthesis", J Neurosci, 22, pp.3090~3099 (2002)[DOI]
- Spillantini MG, "The alpha-synucleinopathies: Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy", Ann N Y Acad Sci, 920, pp.16~27 (2000)
- Braak H, "Staging of the intracerebral inclusion body pathology associated with idiopathic Parkinson's disease (preclinical and clinical stages)", J Neurol, 249(Suppl 3), pp.III (2002), 1~III[DOI]
- Mollenhauer B, "<TEX>${\alpha}$<", TEX>-Synuclein and tau concentrations in cerebrospinal fluid of patients presenting with parkinsonism: a cohort study, 2011, pp.10, 230~240
- Beyer K, "Identification and characterization of a new alpha-synuclein isoform and its role in Lewy body diseases", Neurogenetics, 9, pp.15~23 (2008)[DOI]
- Gao R, "CSF biomarkers and its associations with 18F-AV133 cerebral VMAT2 binding in Parkinson's disease-a preliminary report", PLoS One, 11, pp.e0164762~ (2016)[DOI]
- Spillantini MG, "Alpha-synuclein in Lewy bodies", Nature, 388, pp.839~840 (1997)[DOI]
- Edwards TL, "Genome-wide association study confirms SNPs in SNCA and the MAPT region as common risk factors for Parkinson disease", Ann Hum Genet, 74, pp.97~109 (2010)[DOI]
- Parkinson Progression Marker Initiative, "The Parkinson Progression Marker Initiative (PPMI)", Prog Neurobiol, 95, pp.629~635 (2011)[DOI]
- Garcia-Gomez FJ, "Elaboration of the SPM template for the standardization of SPECT images with 123I-Ioflupane", Rev Esp Med Nucl Imagen Mol, 32, pp.350~356 (2013)
- Tzourio-Mazoyer N, "Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain", Neuroimage, 15, pp.273~289 (2002)[DOI]
- Mollenhauer B, "Longitudinal CSF biomarkers in patients with early Parkinson disease and healthy controls", Neurology, 89, pp.1959~1969 (2017)[DOI]
- Heckman MG, "Parkinson's disease susceptibility variants and severity of Lewy body pathology", Parkinsonism Relat Disord, 44, pp.79~84 (2017)[DOI]
- Caspell-Garcia C, "Multiple modality biomarker prediction of cognitive impairment in prospectively followed de novo Parkinson disease", PLoS One, 12, pp.e0175674~ (2017)[DOI]
- Chen PS, "Effects of C825T polymorphism of the GNB3 gene on availability of dopamine transporter in healthy volunteers--a SPECT study", Neuroimage, 56, pp.1526~1530 (2011)[DOI]
- van de Giessen E, "Striatal dopamine transporter availability associated with polymorphisms in the dopamine transporter gene SLC6A3", J Nucl Med, 50, pp.45~52 (2009)
- van Dyck CH, "Increased dopamine transporter availability associated with the 9-repeat allele of the SLC6A3 gene", J Nucl Med, 46, pp.745~751 (2005)
- Fazio L, "D2 receptor genotype and striatal dopamine signaling predict motor cortical activity and behavior in humans", Neuroimage, 54, pp.2915~2921 (2011)[DOI]
- Locascio JJ, "Association between <TEX>${\alpha}$<", TEX>-synuclein blood transcripts and early, neuroimaging-supported Parkinson's disease, 2015, pp.138, 2659~2671
- Emamzadeh FN, "Alpha-synuclein structure, functions, and interactions", J Res Med Sci, 21, pp.29~ (2016)[DOI]
- Wong YC, "<TEX>${\alpha}$<", TEX>-synuclein toxicity in neurodegeneration: mechanism and therapeutic strategies, 2017, pp.23, 1~13
- Rhinn H, "Alternative <TEX>${\alpha}$<", TEX>-synuclein transcript usage as a convergent mechanism in Parkinson's disease pathology, 2012, pp.3, 1084~
