Tomm40

BACKGROUND: The 523 poly-T length polymorphism (rs10524523) in TOMM40 has been reported to influence longitudinal cognitive test performance within APOE ε3/3 carriers. The results from prior studies are inconsistent. It is also unclear whether specific APOE and TOMM40 genotypes contribute to heterogeneity in longitudinal cognitive performance during the preclinical stages of AD. OBJECTIVES: To determine the effects of these genes on longitudinal cognitive change in early preclinical stages of AD, we used the clinical trial data from the recently concluded TOMMORROW study to examine the effects of APOE and TOMM40 genotypes on neuropsychological test performance...

Both the APOE ε4 and TOMM40 rs10524523 ("523") genes have been associated with risk for Alzheimer's disease (AD) and neuroimaging biomarkers of AD. No studies have investigated the relationship of TOMM40'523-APOE ε4 on the structural complexity of the brain in AD individuals. We quantified brain morphology and multiple cortical attributes in individuals with mild cognitive impairment (MCI) and AD, then tested whether APOE ε4 or TOMM40 poly-T genotypes were related to AD morphological biomarkers in cognitively unimpaired (CU) and MCI/AD individuals...

BACKGROUND: TOMM40 '523 has been associated with cognitive performance and risk for developing Alzheimer's disease independent of the effect of APOE genotype. Few studies have considered the longitudinal effect of this genotype on change in cognition over time. OBJECTIVE: Our objective was to evaluate the relationship between TOMM40 genotype status and change in cognitive performance in the TOMMORROW study, which was designed to prospectively evaluate an algorithm that includes TOMM40 '523 for genetic risk for conversion to mild cognitive impairment...

Alzheimer's Disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous. Here, we investigated the association between AD and both common variants and aggregates of rare coding and noncoding variants in 13,371 individuals of diverse ancestry with whole genome sequence (WGS) data. Pooled-population analyses identified genetic variants in or near APOE, BIN1 , and LINC00320 significantly associated with AD (p < 5×10 -8 ). Population-specific analyses identified a haplotype on chromosome 14 including PSEN1 associated with AD in Hispanics, further supported by aggregate testing of rare coding and noncoding variants in this region...

BACKGROUND: As an important regulatory mechanism to remove damaged mitochondria and maintain the balance between internal and external cells, mitochondrial autophagy plays a key role in the progression and treatment of cancer Onishi (EMBO J 40(3): e104705, 2021). The purpose of this study is to comprehensively analyze the role of mitochondrial autophagy-related genes in the progression of gastric cancer (GC) by RNA sequencing (RNA-seq) and single-cell RNA sequencing (scRNA-seq). METHODS: GSE26942, GSE54129,GSE66229,GSE183904 and other data sets were obtained by GEO databases...

Alzheimer's disease (AD) is the most common neurodegenerative disease, with a complex genetic background. Apart from rare, familial cases, a combination of multiple risk loci contributes to the susceptibility of the disease. Genome-wide association studies (GWAS) have identified numerous AD risk loci. Changes in cerebrospinal fluid (CSF) biomarkers and imaging techniques can detect AD-related brain changes before the onset of clinical symptoms, even in the presence of preclinical mild cognitive impairment. In this study, we aimed to assess the associations between SNPs in well-established GWAS AD risk loci and CSF biomarker levels or cognitive test results in Slovenian patients with cognitive decline...

BACKGROUND: Red wine and dairy products have been staples in human diets for a long period. However, the impact of red wine and dairy intake on brain network activity remains ambiguous and requires further investigation. METHODS: This study investigated the associations between dairy and red wine consumption and seven neural networks' connectivity with functional magnetic resonance imaging (fMRI) data from a sub-cohort of the UK Biobank database. Linear mixed models were employed to regress dairy and red wine consumption against the intrinsic functional connectivity for each neural network...

BACKGROUND: The human chromosome 19q13.32 is a gene rich region and has been associated with multiple phenotypes, including late onset Alzheimer's disease (LOAD) and other age-related conditions. OBJECTIVE: Here we developed the first humanized mouse model that contains the entire TOMM40 and APOE genes with all intronic and intergenic sequences including the upstream and downstream regions. Thus, the mouse model carries the human TOMM40 and APOE genes and their intact regulatory sequences...

The Apolipoprotein E ( APOE) locus has garnered significant clinical interest because of its association with Alzheimer's disease (AD) and longevity. This genetic association appears across multiple genes in the APOE locus. Despite the apparent differences between AD and longevity, both conditions share a commonality of aging-related changes in mitochondrial function. This commonality is likely due to accumulative biological effects partly exerted by the APOE locus. In this study, we investigated changes in mitochondrial structure/function-related markers using oxidative stress-induced human cellular models and postmortem brains (PMBs) from individuals with AD and normal controls...

BACKGROUND: Statins are the drugs most commonly used for lowering plasma low-density lipoprotein (LDL) cholesterol levels and reducing cardiovascular disease risk. Although generally well tolerated, statins can induce myopathy, a major cause of non-adherence to treatment. Impaired mitochondrial function has been implicated as a cause of statin-induced myopathy, but the underlying mechanism remains unclear. We have shown that simvastatin downregulates transcription of TOMM40 and TOMM22 , genes that encode major subunits of the translocase of outer mitochondrial membrane (TOM) complex which is responsible for importing nuclear-encoded proteins and maintaining mitochondrial function...

BACKGROUND: The cause of the most common form of dementia, sporadic Alzheimer's disease (AD), remains unknown. This may reflect insufficiently powered studies to date for this multi-factorial disorder. The UK Biobank dataset presents a unique opportunity to rank known risk factors and determine novel variables. METHODS: A custom machine learning approach for high dimensionality data was applied to explore prospectively associations between AD in a sub-cohort of 156,209 UK Biobank participants aged 60-70 including more than 2,090 who were subsequently diagnosed with AD...

The present study investigated the effects of low ethanol exposure on bovine oocytes. Cumulus-oocyte complexes (COCs) were aspirated for the antral follicles of slaughterhouse-derived ovaries. These COCs were incubated in maturation medium containing 0, 0.1, and 0.2% ethanol for 21 h and subjected to fertilization and in vitro development, and then the rates of nuclear maturation, mitochondrial DNA copy number (Mt-cn) and protein (TOMM40), ATP content and lipid content in oocyte, fertilization, and blastulation were examined...

In-depth studies on the pathogenesis of endometrial cancer (EC) are critical because of the increasing global incidence of EC. Mitophagy, a mitochondrial quality control process, plays an important role in carcinogenesis and tumor progression. This study aimed to develop a novel mitophagy-based signature to predict the tumorigenesis and prognosis of EC. Data was downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases, and 29 mitophagy-related genes were downloaded from the Pathway Unification Database...

BACKGROUND: Short structural variants (SSVs), including insertions/deletions (indels), are common in the human genome and impact disease risk. The role of SSVs in late-onset Alzheimer's disease (LOAD) has been understudied. In this study, we developed a bioinformatics pipeline of SSVs within LOAD-genome-wide association study (GWAS) regions to prioritize regulatory SSVs based on the strength of their predicted effect on transcription factor (TF) binding sites. METHODS: The pipeline utilized publicly available functional genomics data sources including candidate cis-regulatory elements (cCREs) from ENCODE and single-nucleus (sn)RNA-seq data from LOAD patient samples...

Choreoacanthocytosis, one of the forms of neuroacanthocytosis, is caused by mutations in vacuolar protein sorting-associated protein A (VPS13A), and is often misdiagnosed with other form of neuroacanthocytosis with discrete genetic defects. The phenotypic variations among the patients with VPS13A mutations significantly obfuscates the understanding of the disease and treatment strategies. In this study, two unrelated cases were identified, exhibiting the core phenotype of neuroacanthocytosis but with considerable clinical heterogeneity...

Amyloid-β (Aβ) peptide is accumulated in the mitochondria and has been shown to play a central role in the development of Alzheimer's disease (AD). It has been shown that exposure of neurons to aggregated Aβ can result in damaged mitochondria and dysregulated mitophagy, indicating that changes in the Aβ content of mitochondria may affect the levels of mitophagy and interfere with the progression of AD. However, the direct influence of mitochondrial Aβ on mitophagy has not been elucidated...

BACKGROUND AND AIMS: As a result of increasing numbers of studies most recently, mitophagy plays a vital function in the genesis of cancer. However, research on the predictive potential and clinical importance of mitophagy-related genes (MRGs) in hepatocellular carcinoma (HCC) is currently lacking. This study aimed to uncover and analyze the mitophagy-related diagnostic biomarkers in HCC using machine learning (ML), as well as to investigate its biological role, immune infiltration, and clinical significance...

Translocase of outer mitochondrial membrane 40 ( TOMM40 ) is located in the outer membrane of mitochondria. TOMM40 is essential for protein import into mitochondria. TOMM40 genetic variants are believed to increase the risk of Alzheimer's disease (AD) in different populations. In this study, three exonic variants (rs772262361, rs157581, and rs11556505) and three intronic variants (rs157582, rs184017, and rs2075650) of the TOMM40 gene were identified from Taiwanese AD patients using next-generation sequencing...

Proxy phenotypes allow for the utilization of genetic data from large population cohorts to analyze late-onset diseases by using parental diagnoses as a proxy for genetic disease risk. Proxy phenotypes based on parental diagnosis status have been used in previous studies to identify common variants associated with Alzheimer's disease. As of yet, proxy phenotypes have not been used to identify genes associated with Alzheimer's disease through rare variants. Here we show that a proxy Alzheimer's disease/dementia phenotype can capture known Alzheimer's disease risk genes through rare variant aggregation...

We aimed to create a mitophagy-related risk model via data mining of gene expression profiles to predict prognosis in uveal melanoma (UM) and develop a novel method for improving the prediction of clinical outcomes. Together with clinical information, RNA-seq and microarray data were gathered from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. ConsensusClusterPlus was used to detect mitophagy-related subgroups. The genes involved with mitophagy, and the UM prognosis were discovered using univariate Cox regression analysis...