Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P10636 (tau protein)
 5,110 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Frontotemporal dementia (FTD) is a common neurodegenerative disorder and is connected with about 10% of all dementias. In approximately half of all FTD cases, a positive family history has been reported. To date, several mutations at the tau protein gene (MAPT) were identified causing familial and sporadic FTD. Extensive polymorphic variability at the MAPT gene has also been shown to be a risk factor in progressive supranuclear palsy (PSP). The recently described gene Saitohin (STH), located in the intron 9 of MAPT gene, was also reported to be polymorphic. In the present study 23 unrelated Polish patients with clinically defined sporadic and familial FTD were screened for mutations at the MAPT gene. No pathogenic mutations were found in the group. Several novel silent intronic and exonic mutations were identified, most of them associated with two common haplotypes. In the reported group no correlation between extended MAPT haplotype and APOE genotype was determined. There was also no observed relation between age of onset and APOE status. At the STH gene only a common polymorphic change was found. It is postulated that MAPT mutations are not connected with most of the FTD cases in the Polish population.
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PMID:Mutation screening of the MAPT and STH genes in Polish patients with clinically diagnosed frontotemporal dementia. 1282 37

The saitohin (STH) gene is located in intron 9 of the tau protein gene. It has been postulated that the R allele of Q7R polymorphism at the Saitohin gene is over-represented in the homozygous state in sporadic Alzheimer's disease (AD). Tau protein was implicated in AD pathophysiology and the tau gene haplotype is probably connected with sporadic late-onset Parkinson's disease (PD). We analyzed the STH polymorphism and tau gene haplotype in 100 clinically diagnosed AD cases, 100 PD cases and 100 age-matched healthy controls. We found that the R allele of the STH gene is associated with the H2 haplotype of tau in all cases. Additionally we observed no correlation between R allele frequency and AD or PD.
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PMID:Strong association between Saitohin gene polymorphism and tau haplotype in the Polish population. 1293 19

Neurofibrillary tangles, containing hyperphosphorylated microtubule-associated protein tau, are one of the major pathological hallmarks of Alzheimer's disease. To investigate a possible association between tau genotypes and the risk of Alzheimer's disease, we screened for polymorphisms in the tau gene and found a novel polymorphism IVS11 + 90G --> A. A case-control study (874 patients and 678 controls) showed a significant association between possession of the A allele and male Alzheimer's disease with early-onset (age of onset before 65, odds ratio = 2.65; 95% confidence interval 1.30-5.42), suggesting that age and gender modify the risk effect. However, we failed to replicate the reported association between the Saitohin gene located in the tau intron 9 and Japanese Alzheimer's disease.
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PMID:Association between tau polymorphism and male early-onset Alzheimer's disease. 1510 53

Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are sporadic neurodegenerative diseases presenting as atypical parkinsonian disorders, characterized by the presence of tau-positive neurofibrillary tangles. Recently, an extended haplotype (H1E) of 787.6 kb that comprises several genes including MAPT showed increased association with PSP. The objective of this study was to determine the size of the H1E haplotype associated with PSP and CBD in different populations and to identify specific subhaplotypes in the background of H1E haplotype. Nineteen single nucleotide polymorphisms (SNPs) in the 17q21 region were genotyped in two case-control samples. The SNPs that were associated with higher risk for the disease in the homozygous state delimit a region of more that 1 Mb. Haplotype analyses in the Spanish sample showed that the most frequent haplotype found among the patients (H1E'), which extends 1.04 Mb and contains several genes such as MAPT, CRHR1, IMP5, Saitohin, WTN3, and NSF. A specific subhaplotype (H1E'A) was present in 16% of PSP patients but was not observed in the controls. Furthermore, the H2E'A haplotype, was rarely present in the disease group suggesting that it plays a protective role. The identification of these specific subhaplotypes that modify risk for PSP/CBD supports the hypothesis that a pathogenic allele exists in a subgroup of PSP patients.
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PMID:Novel haplotypes in 17q21 are associated with progressive supranuclear palsy. 1529 77

Aberrant phosphorylated tau is the major component of the neurofibrillary tangles in Alzheimer's disease (AD) brains. Glycogen synthase kinase-3beta (GSK-3beta) phosphorylates tau protein, and increased GSK-3beta expression has been associated with neurofibrillary tangles. Saitohin (STH) is a recently identified protein that shares tissue expression pattern with tau, and previous evidence in the Spanish population indicated that a polymorphism at codon 7 (Q7R) of the STH gene was associated with late-onset AD. Since both GSK-3beta and STH are related to tau, we examined the association between a polymorphism in the promoter region (-50) of the GSK-3beta gene and AD, either through an independent effect or through interaction with the STH (Q7R) polymorphism, in a well-defined group of 333 sporadic AD patients and 307 control subjects from Spain. The current study reveals that GSK-3beta (-50) TT genotype is associated with an increased risk (OR 1.99, p = 0.003) for late-onset (after the age of 72 years) AD. Our results indicate that both the GSK-3beta (-50) and STH (Q7R) polymorphisms increase the risk of late-onset (subjects >72 years) AD, although they appear to be independent and thus not to interact synergistically.
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PMID:Association between glycogen synthase kinase-3beta genetic polymorphism and late-onset Alzheimer's disease. 1642 84

About 15% of patients with a clinical phenotype of Angelman syndrome (AS) have an unknown etiology. We report a patient with features reminiscent of AS, including a pattern of characteristic facial anomalies as well as speech impairment, developmental delay and frequent laughter. In addition, the patient had features not commonly associated with AS such as heart malformations and scoliosis. She was negative in SNURF-SNRPN exon 1 methylation studies and the G-banded karyotype was normal. Array-based comparative genomic hybridization disclosed a deletion of maximally 1 Mb at 17q21.31. The deleted region contains the MAPT gene, implicated in late onset neurodegenerative disorders, and the STH and NP_056258.1 genes. Another gene, such as CRHR1, might also be included based on maximum possible size of the deletion. We suggest that microdeletions within the 17q21.31 segment should be considered as a possible cause of phenotypes resembling AS, particularly when easily controlled seizures and/or cardiac abnormalities are also present.
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PMID:A 17q21.31 microdeletion encompassing the MAPT gene in a mentally impaired patient. 1671 56

Deregulation of tau mRNA splicing may contribute to causing progressive supranuclear palsy (PSP). The inclusion of exon 10 produces tau protein isoforms containing all four microtubule-binding repeats (4R). Its exclusion gives rise to isoforms with three microtubule-binding repeats (3R). Alternative splicing of exons 2 and 3 produces the 0N, 1N or 2N protein isoforms. Saitohin (STH) is a nested gene included in intron 9 of tau. It has an unknown function, but could also be involved in the pathological process associated with PSP. We used real-time PCR to investigate the level of expression of tau mRNA isoforms and STH mRNA in the frontal cortex and globus pallidus of PSP patients' brains. mRNA levels were compared with those in the brains of two controls groups: healthy controls and Alzheimer's disease patients (AD). The 4R/3R mRNA ratio was significantly higher in the globus pallidus of PSP patients than in controls. The 0N mRNA isoform levels were statistically higher in the frontal cortex and globus pallidus of AD patients and were borderline higher in the globus pallidus of PSP patients than controls. In addition, when all samples were taken into account (PSP+AD+controls), a significant correlation was found between the 4R/3R mRNA tau ratio and STH expression. This correlation was stronger in the globus pallidus than in the frontal cortex. Our results suggest that abnormalities in the alternative splicing of the tau gene are involved in the molecular mechanism related to PSP pathogenesis. Such abnormalities cause an increase in the 4R/3R ratio and may lead to an overexpression of 0N tau isoforms.
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PMID:Tau and saitohin gene expression pattern in progressive supranuclear palsy. 1732 Aug 31

Saitohin (STH) is located in the intron of the human gene for microtubule-associated protein tau. Q7R polymorphism has been identified in the STH gene. Some neurodegenerative disorders were found to be associated with the presence of certain STH allele. This study genotyped 37 subjects with diagnosis of Huntington's disease, but lacking mutations in HD, PRNP, JPH-3, and FTL genes for STH polymorphism. It was determined that Q allele of STH gene was over-represented in a tested group of patients (P > Pt). Over-representation of Q allele in a group of patients might be considered as genetic risk factor for HD like diseases.
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PMID:HD phenocopies--possible role of Saitohin gene. 1830 12

Multiple genetic variants may contribute to the risk of developing Alzheimer's disease. We have analyzed polymorphisms in 9 genes to determine whether particular combinations would contribute to this risk. The genes were APOE, LDLr, CST3, CTSD, TNF, BACE1, MAPT, STH, eNOS, and TFCP2. Three risk groups for the disease were identified. Risk group I was younger, was heterozygous for the CST3 (GA), CTSD2936 (AG), TNF -308 (AG) genetic variants. Risk group II was older, was homozygous for the -427 APOE promoter polymorphism (TT), and heterozygous for the MAPT deletion and for the STH variant (QR). Group III had both the youngest and oldest subjects, were heterozygous for the -863 (AC) and -1031 (CT) TNF promoter polymorphisms. All three groups carried the APOE 4 allele and were heterozygous for both BACE1 polymorphisms. The control groups were carriers of the APOE 3 allele and were homozygous for the BACE1 genetic variants.
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PMID:Cluster analysis of risk factor genetic polymorphisms in Alzheimer's disease. 1830 33

Serotonergic transmission impairment and abnormal phosphorylation of tau protein have been implicated in the physiopathology of Alzheimer's disease (AD) and frontotemporal lobar dementia (FTLD). Associations between a functional polymorphism (5-HTTLPR), in the promoter region of the serotonin transporter gene, and susceptibility to sporadic AD and FTLD have been reported. A polymorphism (Q7R) in saitohin gene inside the microtubule-associated protein tau gene has also been related to dementia. To determine the possible role of the two polymorphisms in susceptibility to AD and FTLD, we performed a case-control study collecting 218 Italian sporadic dementia patients and 54 controls. We found a significant excess of 5-HTTLPR short alleles and an interaction between 5-HTTLPR and Q7R polymorphisms in demented subjects. Our study confirms the role of 5-HTTLPR as a potential susceptibility factor for sporadic dementia in the Italian population, and suggests a possible interaction between 5-HTTLPR and Q7R polymorphisms in neurodegenerative diseases.
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PMID:Serotonin transporter and saitohin genes in risk of Alzheimer's disease and frontotemporal lobar dementia: preliminary findings. 2085 9


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