ArticleAnnals of neurology2009
Single-cell expression profiling of dopaminergic neurons combined with association analysis identifies pyridoxal kinase as Parkinson's disease gene.
Article in Annals of neurology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Novel Insights Into the Causal Effects and Shared Genetics Between Body Fat and Parkinson Disease.CNS neuroscience & therapeutics · 2024Pooled it
- Transcriptomic profiling of Parkinson's disease brains reveals disease stage specific gene expression changes.Acta neuropathologica · 2023Article
- Review
- Could Vitamins Have a Positive Impact on the Treatment of Parkinson's Disease?Brain sciences · 2023Review
- Somatic Mutations Detected in Parkinson Disease Could Affect Genes With a Role in Synaptic and Neuronal Processes.Frontiers in aging · 2022Article
- Synucleinopathy-associated pathogenesis in Parkinson's disease and the potential for brain-derived neurotrophic factor.NPJ Parkinson's disease · 2021Review
- The Implications of ncRNAs in the Development of Human Diseases.Non-coding RNA · 2021Review
- Deficiencies in vesicular transport mediated by TRAPPC4 are associated with severe syndromic intellectual disability.Brain : a journal of neurology · 2020Article
- Review
- A loss of Pdxk model of Parkinson disease in Drosophila can be suppressed by Buffy.BMC research notes · 2017Article
- Diquat causes caspase-independent cell death in SH-SY5Y cells by production of ROS independently of mitochondria.Archives of toxicology · 2015Article
- Altered Expression Patterns of Inflammation-Associated and Trophic Molecules in Substantia Nigra and Striatum Brain Samples from Parkinson's Disease, Incidental Lewy Body Disease and Normal Control Cases.Frontiers in neuroscience · 2015Article
- Microarray gene expression profiling of neural tissues in bovine spastic paresis.BMC veterinary research · 2013Article
- Single cell genomics of the brain: focus on neuronal diversity and neuropsychiatric diseases.Current genomics · 2012Article
- Current status and future directions of gene expression profiling in Parkinson's disease.Neurobiology of disease · 2012Review
- Dopaminergic axon guidance: which makes what?Frontiers in cellular neuroscience · 2012Article
- High dimensional endophenotype ranking in the search for major depression risk genes.Biological psychiatry · 2012Article
- Biomarker candidates of neurodegeneration in Parkinson's disease for the evaluation of disease-modifying therapeutics.Journal of neural transmission (Vienna, Austria : 1996) · 2012Review
- A genome-wide linkage screen in the Amish with Parkinson disease points to chromosome 6.Annals of human genetics · 2011Article
- A Novel Microduplication in the Neurodevelopmental Gene SRGAP3 That Segregates with Psychotic Illness in the Family of a COS Proband.Case reports in genetics · 2011Article
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31 authors at 12 institutions in 3 countries.
Funding
Abstract
objectiveThe etiology of Parkinson disease (PD) is complex and multifactorial, with hereditary and environmental factors contributing. Monogenic forms have provided molecular clues to disease mechanisms but genetic modifiers of idiopathic PD are still to be determined.
methodsWe carried out whole-genome expression profiling of isolated human substantia nigra (SN) neurons from patients with PD vs. controls followed by association analysis of tagging single-nucleotide polymorphisms (SNPs) in differentially regulated genes. Association was investigated in a German PD sample and confirmed in Italian and British cohorts.
resultsWe identified four differentially expressed genes located in PD candidate pathways, ie, MTND2 (mitochondrial, p = 7.14 x 10(-7)), PDXK (vitamin B6/dopamine metabolism, p = 3.27 x 10(-6)), SRGAP3 (axon guidance, p = 5.65 x 10(-6)), and TRAPPC4 (vesicle transport, p = 5.81 x 10(-6)). We identified a DNA variant (rs2010795) in PDXK associated with an increased risk of PD in the German cohort (p = 0.00032). This association was confirmed in the British (p = 0.028) and Italian (p = 0.0025) cohorts individually and reached a combined value of p = 1.2 x 10(-7) (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.18-1.44).
interpretationWe provide an example of how microgenomic genome-wide expression studies in combination with association analysis can aid to identify genetic modifiers in neurodegenerative disorders. The detection of a genetic variant in PDXK, together with evidence accumulating from clinical studies, emphasize the impact of vitamin B6 status and metabolism on disease risk and therapy in PD.
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