Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A number of gene variants or single nucleotide polymorphisms (SNPs) have been shown to modulate the risk of Parkinson's disease (PD). These variants are identified from genetic association studies of familial PD and candidate genes, and from genome wide association studies (GWAS). These include REP1 dinucleotide repeat polymorphism within the promoter region of the SNCA gene, and SNPs within the vicinity of SNCA and LRRK2 genes. A number of exonic variants of LRRK2 (G2385R, R1628P, S1647T, M1646T, A419V, R1398H, N551K, Y2189C) have been shown to influence PD risk in various ethnic populations. Numerous GWAS linked loci including BST1 (bone marrow stromal cell antigen 1), PARK16 (parkinson disease 16 susceptibility), GAK (cyclin G associated kinase), and HLA (human leukocyte antigen) have also been identified. The genetic variants have differential effect on PD risk in Eastern and Western populations. Knowing the basis behind ethnic-specific variances would further our understanding of the pathophysiologic mechanisms and help planning of genetic testing programmes.
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PMID:Genetic variants in sporadic Parkinson's disease: East vs West. 2216 57

Parkinson disease (PD) is a complex neurodegenerative disorder with largely unknown genetic mechanisms. While the degeneration of dopaminergic neurons in PD mainly takes place in the substantia nigra pars compacta (SN) region, other brain areas, including the prefrontal cortex, develop Lewy bodies, the neuropathological hallmark of PD. We generated and analyzed expression data from the prefrontal cortex Brodmann Area 9 (BA9) of 27 PD and 26 control samples using the 44K One-Color Agilent 60-mer Whole Human Genome Microarray. All samples were male, without significant Alzheimer disease pathology and with extensive pathological annotation available. 507 of the 39,122 analyzed expression probes were different between PD and control samples at false discovery rate (FDR) of 5%. One of the genes with significantly increased expression in PD was the forkhead box O1 (FOXO1) transcription factor. Notably, genes carrying the FoxO1 binding site were significantly enriched in the FDR-significant group of genes (177 genes covered by 189 probes), suggesting a role for FoxO1 upstream of the observed expression changes. Single-nucleotide polymorphisms (SNPs) selected from a recent meta-analysis of PD genome-wide association studies (GWAS) were successfully genotyped in 50 out of the 53 microarray brains, allowing a targeted expression-SNP (eSNP) analysis for 52 SNPs associated with PD affection at genome-wide significance and the 189 probes from FoxO1 regulated genes. A significant association was observed between a SNP in the cyclin G associated kinase (GAK) gene and a probe in the spermine oxidase (SMOX) gene. Further examination of the FOXO1 region in a meta-analysis of six available GWAS showed two SNPs significantly associated with age at onset of PD. These results implicate FOXO1 as a PD-relevant gene and warrant further functional analyses of its transcriptional regulatory mechanisms.
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PMID:Gene expression profiles in Parkinson disease prefrontal cortex implicate FOXO1 and genes under its transcriptional regulation. 2276 92