BMC Medical Genomics最新文献

Background: Congenital biliary dilatation (CBD) is a prevalent congenital biliary disease in children, particularly in Asian populations, yet its etiology remains poorly understood. This study aimed to investigate the genome-wide DNA methylation profile in the peripheral blood of children with CBD to identify potential epigenetic mechanisms involved in its pathogenesis.

Methods: Genome-wide DNA methylation profiles were compared between whole blood samples from 37 children with CBD and 24 healthy controls using the Illumina Infinium Human MethylationEPIC (850 K) BeadChip. Bioinformatic analyses were performed to identify differentially methylated positions (DMPs) and regions (DMRs), and functional enrichment analysis was conducted on associated genes.

Results: We identified 24,230 differentially methylated sites associated with 5,863 genes. Among these, 8,313 sites were hypermethylated and 15,917 were hypomethylated in CBD patients compared to controls. 54 significant differentially methylated regions (DMRs) were also detected. Functional enrichment analysis revealed that the differentially methylated genes were significantly enriched in key biological pathways, most notably the T cell receptor signaling pathway.

Conclusion: This study presents the first comprehensive analysis of genome-wide DNA methylation in CBD, revealing significant epigenetic alterations in peripheral blood. These findings suggest that aberrant DNA methylation, particularly in genes regulating immune pathways, may play a critical role in the development of CBD and could provide valuable insights for identifying novel diagnostic biomarkers.

Background: CARS1 loss of function compound heterozygous or homozygous variants have been reported in five individuals to cause a neurodevelopmental phenotype that includes microcephaly and brittle hair and nails. Additional multisystem involvement in these five people have included neurologic, cardiac, ophthalmologic and endocrine problems.

Case presentation: We report a sixth person with novel compound heterozygous variants in CARS1. In addition to the previously reported features such as intellectual disability, neurologic features, microcephaly and hair abnormalities, this patient had persistent hypoglycemia due to congenital hyperinsulinism.

Conclusions: This report identifies two novel variants in CARS1 and expands the phenotype of this multisystem disorder to include congenital hyperinsulinism.

Background: Intrauterine growth restriction (IUGR) with rapid postnatal catch-up growth has been associated with adipose tissue inflammation and metabolic dysfunction. The long-term persistence of these abnormalities and their relationship with different catch-up growth patterns remain unclear.

Methods: To investigate the long-term metabolic consequences of IUGR in relation to different catch-up growth patterns. An experimental animal study using a rat model of IUGR induced by maternal protein restriction during gestation. Abdominal adipose tissue transcriptome profiles in male rats were analyzed at 3 and 9 months of age, considering variations in catch-up growth patterns. The primary outcomes included markers of adipose tissue inflammation and metabolic function.

Results: Among IUGR offspring, approximately 50% demonstrated slow catch-up growth and remained undernourished at 3 months of age. Transcriptome analysis revealed persistent adipose tissue inflammation and metabolic alterations that progressed with age. These abnormalities were present in both rapid and slow catch-up growth groups, although offspring with rapid catch-up growth exhibited more adverse manifestations.

Conclusion: IUGR was associated with long-term adipose tissue inflammation and metabolic dysfunction, independent of catch-up growth pattern. These findings suggest that IUGR may have lasting metabolic consequences regardless of postnatal growth trajectory.

Background: As the building blocks of proteins and precursors of many other important compounds, amino acids play a vital role in the biochemical processes needed to sustain life. The branched-chain amino acids (BCAAs) are unique in their structure and function, as they are metabolized in muscle tissue and play important roles in protein synthesis and energy production. However, despite their physiological importance, relatively little integrative research has been conducted into the direct relationships between this class of metabolites and their effect on risk for metabolic diseases.

Methods: Utilizing an integrative PheWAS approach using UK Biobank data, we were able to identify strong, high confidence, metabolite-disease correlations for the three BCAAs: leucine, isoleucine, and valine. Relationships were established through comparison of metabolite level-disease prevalence associations with polygenic scores for BCAAs, followed by Mendelian randomization analysis.

Results: All BCAAs studied demonstrated especially strong relationships with type II diabetes, and robust relationships with obesity, hypertension, sleep apnea, and chronic kidney disease. We illustrate this with a set of metabolite prevalence-disease risk plots that suggest differing potential for disease based on varying levels of branched-chain amino acid metabolites. Similar results are observed with polygenic scores for plasma BCAAs. Mendelian randomization shows positive effects of leucine and isoleucine on hypertension, and either reverse causality or no clear directional relationship for other associations, notably effects of obesity and type II diabetes on all three BCAAs, with limited or borderline evidence for other outcomes.

Conclusions: Overall, the results of our study highlight a relatively unexplored area of metabolite-disease associations and provide a blueprint for uncovering additional relationships using readily available biobank data.

Background: Stomach adenocarcinoma (STAD) poses a major public health challenge across various populations, necessitating the construction of robust models for prognostic prediction and effective clinical therapies. Dysregulation of lactylation, a key regulatory mechanism in cell metabolism and gene expression, can either impede or promote tumor growth and metastasis.

Methods: This study got into the bottom of TCGA-STAD-sourced transcriptome data to profile lactylation-related genes and construct a gene signature through LASSO regression. A nomogram was further created to assess the prognostic performance of this model. Our investigation primarily concentrated on the expression of Dehydrogenase/reductase 7 (DHRS7) in STAD, with the verification of its correlations with clinical characteristics, immune cell infiltration, and cellular signaling pathways.

Results: DHRS7 expressed lower in STAD tissues, and that modulating DHRS7 levels could either promote or inhibit malignant behaviors associated with STAD. In the later stages of tumor progression, DHRS7 appeared to facilitate tumor growth through mechanisms such as immune evasion and activation of PI3K/AKT/mTOR signaling pathways, ultimately contributing to an unfavorable prognosis.

Conclusions: DHRS7 has the potential to shift from acting as a tumor suppressor to functioning as an oncogene in modified TMEs, despite its lower expression levels in STAD tissues relative to normal tissues. This transformation accounts for the association between high DHRS7 expression in the later stages of STAD and a negative prognosis.