PubMed:16315267 JSONTXT

{"project":"PubmedHPO","denotations":[{"id":"T1","span":{"begin":77,"end":86},"obj":"HP_0001300"}],"text":"GSK3B polymorphisms alter transcription and splicing in Parkinson's disease.\nParkinson's disease (PD) is a neurodegenerative disorder characterized by a combination of motor symptoms. We identified two functional single nucleotide polymorphisms in the glycogen synthase kinase-3beta gene (GSK3B). A promoter single nucleotide polymorphism (rs334558) is associated with transcriptional strength in vitro in which the T allele has greater activity. An intronic single nucleotide polymorphism (rs6438552) regulates selection of splice acceptor sites in vitro. The T allele is associated with altered splicing in lymphocytes and increased levels of GSK3B transcripts that lack exons 9 and 11 (GSKDeltaexon9+11). Increased levels of GSKDeltaexon9+11 correlated with enhanced phosphorylation of its substrate, Tau. In a comparison of PD and control brains, there was increased in frequency of T allele (rs6438552) and corresponding increase in GSKDeltaexon9+11 and Tau phosphorylation in PD brains. Conditional logistic regression indicated gene-gene interaction between T/T genotype of rs334558 and H1/H1 haplotype of microtubule-associated protein Tau (MAPT) gene (p = 0.009). There was association between a haplotype (T alleles of both GSK3B polymorphisms) and disease risk after stratification by Tau haplotypes ((H1/H2+H2/H2 individuals: odds ratio, 1.64; p = 0.007; (H1/H1 individuals: odds ratio, 0.68; p \u003c 0.001). Ours results suggest GSK3B polymorphisms alter transcription and splicing and interact with Tau haplotypes to modify disease risk in PD."}

{"project":"DisGeNET5_variant_disease","denotations":[{"id":"16315267-7#88#97#geners6438552","span":{"begin":897,"end":906},"obj":"geners6438552"},{"id":"16315267-7#19#21#diseaseC0030567","span":{"begin":828,"end":830},"obj":"diseaseC0030567"},{"id":"16315267-7#173#175#diseaseC0030567","span":{"begin":982,"end":984},"obj":"diseaseC0030567"}],"relations":[{"id":"88#97#geners643855219#21#diseaseC0030567","pred":"associated_with","subj":"16315267-7#88#97#geners6438552","obj":"16315267-7#19#21#diseaseC0030567"},{"id":"88#97#geners6438552173#175#diseaseC0030567","pred":"associated_with","subj":"16315267-7#88#97#geners6438552","obj":"16315267-7#173#175#diseaseC0030567"}],"text":"GSK3B polymorphisms alter transcription and splicing in Parkinson's disease.\nParkinson's disease (PD) is a neurodegenerative disorder characterized by a combination of motor symptoms. We identified two functional single nucleotide polymorphisms in the glycogen synthase kinase-3beta gene (GSK3B). A promoter single nucleotide polymorphism (rs334558) is associated with transcriptional strength in vitro in which the T allele has greater activity. An intronic single nucleotide polymorphism (rs6438552) regulates selection of splice acceptor sites in vitro. The T allele is associated with altered splicing in lymphocytes and increased levels of GSK3B transcripts that lack exons 9 and 11 (GSKDeltaexon9+11). Increased levels of GSKDeltaexon9+11 correlated with enhanced phosphorylation of its substrate, Tau. In a comparison of PD and control brains, there was increased in frequency of T allele (rs6438552) and corresponding increase in GSKDeltaexon9+11 and Tau phosphorylation in PD brains. Conditional logistic regression indicated gene-gene interaction between T/T genotype of rs334558 and H1/H1 haplotype of microtubule-associated protein Tau (MAPT) gene (p = 0.009). There was association between a haplotype (T alleles of both GSK3B polymorphisms) and disease risk after stratification by Tau haplotypes ((H1/H2+H2/H2 individuals: odds ratio, 1.64; p = 0.007; (H1/H1 individuals: odds ratio, 0.68; p \u003c 0.001). Ours results suggest GSK3B polymorphisms alter transcription and splicing and interact with Tau haplotypes to modify disease risk in PD."}

{"project":"DisGeNET5_gene_disease","denotations":[{"id":"16315267-0#0#5#gene2932","span":{"begin":0,"end":5},"obj":"gene2932"},{"id":"16315267-0#56#75#diseaseC0030567","span":{"begin":56,"end":75},"obj":"diseaseC0030567"}],"relations":[{"id":"0#5#gene293256#75#diseaseC0030567","pred":"associated_with","subj":"16315267-0#0#5#gene2932","obj":"16315267-0#56#75#diseaseC0030567"}],"text":"GSK3B polymorphisms alter transcription and splicing in Parkinson's disease.\nParkinson's disease (PD) is a neurodegenerative disorder characterized by a combination of motor symptoms. We identified two functional single nucleotide polymorphisms in the glycogen synthase kinase-3beta gene (GSK3B). A promoter single nucleotide polymorphism (rs334558) is associated with transcriptional strength in vitro in which the T allele has greater activity. An intronic single nucleotide polymorphism (rs6438552) regulates selection of splice acceptor sites in vitro. The T allele is associated with altered splicing in lymphocytes and increased levels of GSK3B transcripts that lack exons 9 and 11 (GSKDeltaexon9+11). Increased levels of GSKDeltaexon9+11 correlated with enhanced phosphorylation of its substrate, Tau. In a comparison of PD and control brains, there was increased in frequency of T allele (rs6438552) and corresponding increase in GSKDeltaexon9+11 and Tau phosphorylation in PD brains. Conditional logistic regression indicated gene-gene interaction between T/T genotype of rs334558 and H1/H1 haplotype of microtubule-associated protein Tau (MAPT) gene (p = 0.009). There was association between a haplotype (T alleles of both GSK3B polymorphisms) and disease risk after stratification by Tau haplotypes ((H1/H2+H2/H2 individuals: odds ratio, 1.64; p = 0.007; (H1/H1 individuals: odds ratio, 0.68; p \u003c 0.001). Ours results suggest GSK3B polymorphisms alter transcription and splicing and interact with Tau haplotypes to modify disease risk in PD."}

{"project":"PubTator4TogoVar","denotations":[{"id":"30","span":{"begin":340,"end":348},"obj":"SNP"},{"id":"31","span":{"begin":491,"end":500},"obj":"SNP"},{"id":"35","span":{"begin":897,"end":906},"obj":"SNP"},{"id":"38","span":{"begin":1081,"end":1089},"obj":"SNP"}],"attributes":[{"id":"A30","pred":"resolved_to","subj":"30","obj":"tmVar:rs334558;VariantGroup:1;CorrespondingGene:2932;RS#:334558;CorrespondingSpecies:9606"},{"id":"A31","pred":"resolved_to","subj":"31","obj":"tmVar:rs6438552;VariantGroup:0;CorrespondingGene:2932;RS#:6438552;CorrespondingSpecies:9606"},{"id":"A35","pred":"resolved_to","subj":"35","obj":"tmVar:rs6438552;VariantGroup:0;CorrespondingGene:2932;RS#:6438552;CorrespondingSpecies:9606"},{"id":"A38","pred":"resolved_to","subj":"38","obj":"tmVar:rs334558;VariantGroup:1;CorrespondingGene:2932;RS#:334558;CorrespondingSpecies:9606"}],"text":"GSK3B polymorphisms alter transcription and splicing in Parkinson's disease.\nParkinson's disease (PD) is a neurodegenerative disorder characterized by a combination of motor symptoms. We identified two functional single nucleotide polymorphisms in the glycogen synthase kinase-3beta gene (GSK3B). A promoter single nucleotide polymorphism (rs334558) is associated with transcriptional strength in vitro in which the T allele has greater activity. An intronic single nucleotide polymorphism (rs6438552) regulates selection of splice acceptor sites in vitro. The T allele is associated with altered splicing in lymphocytes and increased levels of GSK3B transcripts that lack exons 9 and 11 (GSKDeltaexon9+11). Increased levels of GSKDeltaexon9+11 correlated with enhanced phosphorylation of its substrate, Tau. In a comparison of PD and control brains, there was increased in frequency of T allele (rs6438552) and corresponding increase in GSKDeltaexon9+11 and Tau phosphorylation in PD brains. Conditional logistic regression indicated gene-gene interaction between T/T genotype of rs334558 and H1/H1 haplotype of microtubule-associated protein Tau (MAPT) gene (p = 0.009). There was association between a haplotype (T alleles of both GSK3B polymorphisms) and disease risk after stratification by Tau haplotypes ((H1/H2+H2/H2 individuals: odds ratio, 1.64; p = 0.007; (H1/H1 individuals: odds ratio, 0.68; p \u003c 0.001). Ours results suggest GSK3B polymorphisms alter transcription and splicing and interact with Tau haplotypes to modify disease risk in PD."}

{"project":"PubTatorOnTogoVar","denotations":[{"id":"30","span":{"begin":340,"end":348},"obj":"SNP"},{"id":"31","span":{"begin":491,"end":500},"obj":"SNP"},{"id":"35","span":{"begin":897,"end":906},"obj":"SNP"},{"id":"38","span":{"begin":1081,"end":1089},"obj":"SNP"},{"id":"T1","span":{"begin":340,"end":348},"obj":"SNP"},{"id":"T2","span":{"begin":491,"end":500},"obj":"SNP"},{"id":"T3","span":{"begin":897,"end":906},"obj":"SNP"},{"id":"T4","span":{"begin":1081,"end":1089},"obj":"SNP"}],"attributes":[{"id":"A30","pred":"resolved_to","subj":"30","obj":"tmVar:rs334558;VariantGroup:1;CorrespondingGene:2932;RS#:334558;CorrespondingSpecies:9606"},{"id":"A31","pred":"resolved_to","subj":"31","obj":"tmVar:rs6438552;VariantGroup:0;CorrespondingGene:2932;RS#:6438552;CorrespondingSpecies:9606"},{"id":"A35","pred":"resolved_to","subj":"35","obj":"tmVar:rs6438552;VariantGroup:0;CorrespondingGene:2932;RS#:6438552;CorrespondingSpecies:9606"},{"id":"A38","pred":"resolved_to","subj":"38","obj":"tmVar:rs334558;VariantGroup:1;CorrespondingGene:2932;RS#:334558;CorrespondingSpecies:9606"},{"id":"A1","pred":"resolved_to","subj":"T1","obj":"tmVar:rs334558;VariantGroup:1;CorrespondingGene:2932;RS#:334558;CorrespondingSpecies:9606"},{"id":"A2","pred":"resolved_to","subj":"T2","obj":"tmVar:rs6438552;VariantGroup:0;CorrespondingGene:2932;RS#:6438552;CorrespondingSpecies:9606"},{"id":"A3","pred":"resolved_to","subj":"T3","obj":"tmVar:rs6438552;VariantGroup:0;CorrespondingGene:2932;RS#:6438552;CorrespondingSpecies:9606"},{"id":"A4","pred":"resolved_to","subj":"T4","obj":"tmVar:rs334558;VariantGroup:1;CorrespondingGene:2932;RS#:334558;CorrespondingSpecies:9606"}],"text":"GSK3B polymorphisms alter transcription and splicing in Parkinson's disease.\nParkinson's disease (PD) is a neurodegenerative disorder characterized by a combination of motor symptoms. We identified two functional single nucleotide polymorphisms in the glycogen synthase kinase-3beta gene (GSK3B). A promoter single nucleotide polymorphism (rs334558) is associated with transcriptional strength in vitro in which the T allele has greater activity. An intronic single nucleotide polymorphism (rs6438552) regulates selection of splice acceptor sites in vitro. The T allele is associated with altered splicing in lymphocytes and increased levels of GSK3B transcripts that lack exons 9 and 11 (GSKDeltaexon9+11). Increased levels of GSKDeltaexon9+11 correlated with enhanced phosphorylation of its substrate, Tau. In a comparison of PD and control brains, there was increased in frequency of T allele (rs6438552) and corresponding increase in GSKDeltaexon9+11 and Tau phosphorylation in PD brains. Conditional logistic regression indicated gene-gene interaction between T/T genotype of rs334558 and H1/H1 haplotype of microtubule-associated protein Tau (MAPT) gene (p = 0.009). There was association between a haplotype (T alleles of both GSK3B polymorphisms) and disease risk after stratification by Tau haplotypes ((H1/H2+H2/H2 individuals: odds ratio, 1.64; p = 0.007; (H1/H1 individuals: odds ratio, 0.68; p \u003c 0.001). Ours results suggest GSK3B polymorphisms alter transcription and splicing and interact with Tau haplotypes to modify disease risk in PD."}