BMC Medical Genomics[JOURNAL]
Sun
200 papers
PET/CT and exome sequencing in late onset multiple acyl-CoA dehydrogenase deficiency: a case series and literature review.
Lin DF, Sheng H, Qu Q … +1 more , Liao ZT
BMC Med Genomics · 2025 Oct · PMID 41121198 · Full text
BACKGROUND: Multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare autosomal recessive disorder. Riboflavin-responsive MADD (RR-MADD) represents a treatable subtype, though its molecular mechanisms are incompletely...
BACKGROUND: Multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare autosomal recessive disorder. Riboflavin-responsive MADD (RR-MADD) represents a treatable subtype, though its molecular mechanisms are incompletely characterized. CASE PRESENTATION: Two patients presented to department of Rheumatology, the 3rd Affiliated Hospital of Sun Yet-sen University with progressive proximal muscle weakness. A 2-fluorine-18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan revealed marked metabolic hyperactivity in cervical and paraspinal muscles. Histopathology confirmed lipid storage myopathy, and exome sequencing (ES) identified electron transfer flavoprotein dehydrogenase gene (ETFDH) mutations. Both patients harbored the common variant NM_004453.4:c.250G > A (p.Ala84Thr). Case 1 exhibited homozygosity for this variant and potential XYY syndrome, while Case 2 carried a compound heterozygous mutation including a novel frameshift variant, NM_004453.4: c.265_266del (p. Gln89Valfs*6), and concurrent SLC25A13 mutation linked to adult-onset citrullinemia type II. Riboflavin supplementation achieved complete biochemical remission in both cases. Retrospective analysis for previous reports of homozygous single-locus missense ETFDH gene mutations revealed that patients with mutations in the flavin adenine dinucleotide binding domain (FAD) or the iron-sulfur cluster domain (Fe-S) exhibited a better response to riboflavin and better prognosis. DISCUSSION: 18F-FDG PET/CT is a promising tool for evaluating myopathic involvement in MADD. ES enables rapid and comprehensive diagnosis of MADD and detection of coexisting genetic disorders. The prognosis is related to mutation forms, mutation pathogenicity, and the located structural domain.
Intractable thrombocytopenia in a patient with atypical ataxia-telangiectasia: a case report.
Gu C, Cui Q, Luo W … +3 more , Zhang S, Shu J, Chen S
BMC Med Genomics · 2025 Oct · PMID 41107934 · Full text
BACKGROUND: Ataxia-telangiectasia (A-T) is an infrequent autosomal recessive multisystemic disorder caused by ATM variants. It is characterized by progressive cerebellar ataxia, telangiectasia, susceptibility to malignan...
BACKGROUND: Ataxia-telangiectasia (A-T) is an infrequent autosomal recessive multisystemic disorder caused by ATM variants. It is characterized by progressive cerebellar ataxia, telangiectasia, susceptibility to malignancies and variable immunodeficiency. Patients have phenotypic heterogeneity, especially those with variant A-T form, posing challenges for early diagnosis and intervention. CASE PRESENTATION: Herein we describe an early-onset A-T patient with atypical symptoms, mainly manifested as immunodeficiency and isolated intractable thrombocytopenia, which led to the initial suspicion of immune thrombocytopenia. The patient did not receive a definitive diagnosis of variant A-T until genetic testing was performed and detected a compound heterozygous genotype in ATM. Anti-infective therapy, intravenous immunoglobulin, methylprednisolone as well as treatment of thrombopoietin were administered. The infection was controlled, but therapies had limited effect on the thrombocytopenia. Finally, patient was discharged voluntarily after 17 days of hospitalization with a last platelet count of 29 × 109/L. CONCLUSIONS: This case suggests that A-T should be considered among children with recurrent infections, immunodeficiency and/or thrombocytopenia, even in the absence of typical symptoms, for the sake of reducing incorrect or missed diagnosis. Genetic testing is an efficient tool for early identification and intervention. This report details the phenotype and management of secondary thrombocytopenia in A-T, enhancing clinicians’ insights into the disorder.
Assessment of genetic and metabolite associations of branched chain amino acids with metabolic disease in the UK Biobank using Mendelian randomization.
Konarkowski J, Astore C, Gibson G
BMC Med Genomics · 2025 Oct · PMID 41102794 · Full text
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) a...
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.
Multi-modal characteristics of LncRNA-derived subtypes in colorectal cancer.
Xiong M, Li J, Li X … +4 more , Zhao J, Liu Q, Tu M, Zeng F
BMC Med Genomics · 2025 Oct · PMID 41102785 · Full text
BACKGROUND: The growing knowledge of long non-coding RNA (LncRNA) has suggested the role and predictive potential of LncRNA in cancer, but has not been translated into effective practical tools. The morbidity of colorect...
BACKGROUND: The growing knowledge of long non-coding RNA (LncRNA) has suggested the role and predictive potential of LncRNA in cancer, but has not been translated into effective practical tools. The morbidity of colorectal cancer (CRC) has been declining because of effective screening tools. However, the mechanism of the disease is not well understood. METHODS: The LncRNAs that extracted using univariable Cox analysis were explored for the potential functions and applied for classification of LncRNA-derived subtypes of CRC. Multi-modal data involving microscope to macroscope levels were applied to evaluate the molecular, cell, and medical image characteristics of LncRNA-derived subtypes. Radiomic signature calculated by LASSO regression analysis was utilized for distinguishing the CRC subtypes. The performance of LncRNA and radiomic signature were assessed with respect to its calibration, discrimination, and clinical usefulness. RESULTS: The LncRNA signature composed of 8 LncRNAs significantly associated with prognosis, metabolism, and organismal system showed good performance in patients’ prognosis assessment (AUC, 0.717; time-dependent ROC > 0.71). Patients separated into two subtypes (HRG vs. LRG) based on the LncRNA signature displayed notable prognostic differences (Kaplan-Meier, p < 0.001). Multi-modal analysis indicated obvious heterogeneity between HRG and LRG subgroups, mainly focused on the abnormal enrichment of glycerophospholipid metabolism pathway, different cellular differentiation, and density level characteristics in the tumor region. In addition, the radiomic signature showed good accuracy (AUC, 0.919), discrimination (p < 0.05), and generalization ability (external independent test cohort, p < 0.05) for LncRNA-derived subgroups assessment. CONCLUSION: This study described the multi-modal characteristics landscape of LncRNA-derived subtypes in CRC and strengthened the connection from microscope to macroscope levels.
Intrauterine growth restriction induces persistent adipose inflammation and metabolic abnormalities in rats among various postnatal growth trajectories.
Hu Q, Zhang Z, Yang F … +3 more , Fan Z, Li Y, Li P
BMC Med Genomics · 2025 Oct · PMID 41102701 · Full text
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...
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.
Construction and validation of a lactylation-based gene signature for prognostic assessment and immune infiltration analysis in gastric adenocarcinoma.
Zeng Y, Zhuang G, Xie W … +3 more , Guo S, Wu S, Chen J
BMC Med Genomics · 2025 Oct · PMID 41088300 · Full text
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. Dysr...
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.
Single-cell RNA-seq combined with bulk RNA-seq analysis identifies necroptosis-related genes as therapeutic targets for periodontitis.
Zhu F, Xu M, Xiao Y … +6 more , Yao H, Liu F, Shi S, Huang R, Wu Q, Deng X
BMC Med Genomics · 2025 Oct · PMID 41088263 · Full text
BACKGROUND: Necroptosis, a regulated form of programmed cell death, exacerbates inflammatory responses by releasing damage-associated molecular patterns and inflammatory factors. However, the specific mechanisms underlyi...
BACKGROUND: Necroptosis, a regulated form of programmed cell death, exacerbates inflammatory responses by releasing damage-associated molecular patterns and inflammatory factors. However, the specific mechanisms underlying necroptosis in periodontitis remain largely unclear. This study integrated single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (RNA-seq) data to identify core necroptosis-related genes (NRGs) and validated these findings using external datasets and periodontitis samples collected during our research. METHODS: Overlapping genes were identified through a comparative analysis of 114 NRGs sourced from GeneCards and marker genes specific to various cell types in the single-cell GSE171213 periodontitis dataset. Based on these genes, cells were categorized into high- and low-necroptosis score groups. Key NRGs were identified through intersection analysis of differentially expressed genes in the high necroptosis group using the GSE10334 bulk RNA-seq dataset, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG)/ Gene Ontology (GO) enrichment analysis. Machine learning further identified hub genes associated with the inflammatory response in periodontitis. Consensus clustering analysis, clinical diagnostic model construction, gene set variation analysis, and gene set enrichment analysis were performed based on these hub genes. The model's predictive performance was validated using independent datasets and periodontitis tissue samples. RESULTS: We identified 10 cell types in periodontitis tissues and observed changes in the abundance of various cell populations in affected samples. Furthermore, we selected 35 NRGs differentially expressed in specific cell populations, with neutrophils and macrophages showing higher necroptosis scores. By integrating bulk RNA-seq data, we further identified 29 key NRGs. KEGG/GO analysis indicated their enrichment in inflammatory response signaling pathways. Machine learning highlighted six hub genes (CSF3R, CSF2RB, BTG2, CXCR4, GPSM3, and SSR4), all of which were highly expressed in periodontitis tissues. Consensus clustering based on these genes divided patients with periodontitis into two subgroups with distinct expression profiles. The clinical diagnostic model constructed based on these six key genes exhibited excellent diagnostic performance. Both external independent validation sets and clinical sample tests confirmed high expression of these six key genes in periodontitis tissues. CONCLUSION: Our study identified six hub genes (CSF3R, CSF2RB, BTG2, CXCR4, GPSM3, and SSR4) highly expressed in periodontitis tissues and positively correlated with necroptosis. These genes may serve as therapeutic targets for inflammatory diseases like periodontitis.
An intron SNP rs666088 in SLIT2 increases the risk of acute coronary syndrome in an Iranian population.
Pakdaman P, Naderi N, Farshidi N … +3 more , Farshidi H, Jafari Z, Rahimzadeh M
BMC Med Genomics · 2025 Oct · PMID 41088236 · Full text
BACKGROUND: The Slit guidance Ligand 2 (SLIT2) glycoprotein is of particular interest because of its role in modulating inflammation and the progression of diseases such as atherosclerosis. This study aimed to determine...
BACKGROUND: The Slit guidance Ligand 2 (SLIT2) glycoprotein is of particular interest because of its role in modulating inflammation and the progression of diseases such as atherosclerosis. This study aimed to determine whether SLIT2 polymorphisms can serve as predictive markers for coronary artery disease (CAD) development by investigating its single-nucleotide polymorphisms (SNPs). METHODS: In this case-control study, a total of 321 participants including 217 patients with diagnosed CAD and 104 healthy controls were recruited. Patients were divided into acute coronary syndrome (ACS) (n = 153) and stable angina pectoris (SAP) (n = 64). Allele and genotype frequency of SLIT2 SNP variants rs666088 C > T and rs16869521 A > T were determined using Polymerase Chain Reaction with Sequence-Specific Primers (PCR-SSP). Odds ratios (ORs) were reported along with their 95% confidence intervals (CIs) and P-values. Crude estimates were initially presented, followed by adjusted ORs computed using logistic regression, controlling for potential confounders including age, gender, high-density lipoprotein (HDL) levels, fasting blood sugar (FBS), and smoking status. RESULTS: The frequencies of the T allele of rs666088 were significantly higher in ACS patients compared to healthy controls, and were associated with an increased risk of ACS both before (OR = 1.5, 95% CI = 1.1–2.2, P = 0.01) and after adjustment for confounding factors (OR = 1.3, 95% CI = 1.1–1.9, P = 0.02). Moreover, analysis of ACS subgroups—myocardial infarction (MI) and unstable angina pectoris (UAP), revealed consistent results. However, the allele and genotype frequencies of rs16869521 were not significantly different between patients and controls in any disease categories. CONCLUSIONS: Our study revealed that genetic polymorphism of SLIT2 (rs666088) TT genotype and T allele is the potential host genetic risk factor for ACS. Therefore, SLIT2 (rs666088) genetic variation may be considered as a biomarker for early screening and diagnosis of the disease.
Three intronic variants altering RNA splicing were identified in the CLCN5 gene by minigene assay.
Qiao D, Liu X, Bottillo I … +2 more , Zhang R, Shao L
BMC Med Genomics · 2025 Oct · PMID 41088181 · Full text
BACKGROUND: The Dent disease 1 is a rarely inherited renal tubular disease caused by variants in the CLCN5 gene. Increasing evidence suggests that many intronic variants can affect the normal splicing of pre-mRNA by alte...
BACKGROUND: The Dent disease 1 is a rarely inherited renal tubular disease caused by variants in the CLCN5 gene. Increasing evidence suggests that many intronic variants can affect the normal splicing of pre-mRNA by altering various splicing regulatory signals. Therefore, this study aims to provide novel insights into the impact of intronic variants of CLCN5 on pre-mRNA splicing. METHODS: We analyzed intronic variants of the CLCN5 gene from the Clinvar database, selected four candidate variants using bioinformatics analysis, and identified candidate variants that may alter the splicing of pre-mRNA through minigene assays. RESULTS: Our study revealed that, among four candidate variants, three intronic variants in CLCN5 resulted in splicing alterations(c.603 + 4 A > G, c.727–3 C > A, and c.933 + 3 A > C). Intronic variants c.603 + 4 A > G and c.727–3 C > A induce aberrant splicing that result in partial exon deletions by activating cryptic donor and acceptor splice sites, respectively. In contrast, the c.933 + 3 A > C variant disrupts the classical donor splice site of exon 7, leading to complete exon skipping. CONCLUSIONS: To our knowledge, this is a comprehensive study regarding alterations in pre-mRNA of intronic variants in the causal gene CLCN5 of Dent disease. In addition, we propose the importance of assessing the effect of intronic single nucleotide substitutions on CLCN5 at the mRNA level in the absence of patient RNA samples and show that minigenes functional analysis is valuable for assessing the effect of splicing in vitro.
Identification of radiation-sensitive genes as biomarkers for biodosimetry: an ex vivo analysis of TNFRSF10B, ZMAT3, POLH, and PLK2 in human blood samples.
Boogari M, Mozdarani H, Mahmoudzadeh A … +1 more , Ebrahimi A
BMC Med Genomics · 2025 Oct · PMID 41074151 · Full text
BACKGROUND: Humans are exposed to ionizing radiation (IR), which causes direct and indirect DNA damage. Biodosimetry is a critical component of clinical care following radiation exposure, enabling accurate assessment and...
BACKGROUND: Humans are exposed to ionizing radiation (IR), which causes direct and indirect DNA damage. Biodosimetry is a critical component of clinical care following radiation exposure, enabling accurate assessment and mitigation of health effects. The present study was conducted to investigate the ex vivo expression of the genes TNFRSF10B, ZMAT3, PLK2, and POLH in human peripheral blood samples exposed to X-radiation at doses of 0, 0.5, 2, and 4 Gy at 0, 4, 24, and 48 hours post-exposure. Investigating gene expression dynamics through biodosimetry is a novel approach that may provide insights into gene-specific responses, potentially enhancing the accuracy and sensitivity of radiation dose assessment. MATERIALS AND METHODS: Peripheral blood samples were collected from five healthy volunteers and exposed to 0, 0.5, 2, or 4 Gy radiation with a 6 MV linear accelerator. Following the extraction of RNA and cDNA synthesis, gene expression analysis via qRT‒PCR was performed. These genes were normalized against the housekeeping gene β-actin, and the ΔΔCt method was used for statistical analysis of gene expression. The data were subjected to statistical analysis, and the level of significance (p < 0.05) was determined to test the effects of dose and time on gene expression. RESULTS: The expression of the TNFRSF10B, ZMAT3, POLH, and PLK2 genes was markedly dose- and time-dependent in response to X-ray radiation in vitro. Whole-blood samples irradiated at doses of 0, 0.5, 2, and 4 Gy and analyzed at four time points, 0, 4, 24, and 48 hours, respectively, revealed marked changes in the expression levels of the genes studied, revealing the mechanisms of the response at the cellular level to ionizing radiation. Although minor inter-individual variation in gene expression was observed, it did not significantly affect the overall trends, and the results remained statistically robust. CONCLUSION: These findings highlight a robust biodosimetry framework: TNFRSF10B demonstrated the highest diagnostic performance (AUC = 0.94; sensitivity = 98%; specificity = 75%; cut-off = 1.11), making it a highly reliable biomarker for radiation exposure. PLK2 also exhibited strong discriminative capacity (AUC = 0.84; sensitivity = 90%; specificity = 80%; cut-off =2.5), particularly for minimizing false positives. ZMAT3 (AUC = 0.78; sensitivity/specificity = 75%; cut-off = 3.21) showed balanced early-phase performance, whilePOLH (AUC = 0.73; sensitivity = 80%; specificity = 60%; cut-off = 1.10) may serve as a complementary marker. Collectively, these findings support a multi-gene expression approach for accurate biodosimetric assessment and improved triage following radiation exposure.
The role of genetic polymorphisms on drug response in Alzheimer's disease: a systematic review.
Climacosa FMM, Ornos EDB, Gapaz NCLL … +10 more , Guantia MGR, Cruz JMC, Manalo RVM, Yu ML, Qureshi AP, Carampel AC, Asis JLB, Reyes JCB, Dacasin AB, Anlacan VMM
BMC Med Genomics · 2025 Oct · PMID 41068898 · Full text
Alzheimer’s disease (AD) is the most common neurodegenerative disorder, affecting over 32 million people globally. The variability in treatment response to AD medications is influenced by genetic factors, sex, comorbidit...
Alzheimer’s disease (AD) is the most common neurodegenerative disorder, affecting over 32 million people globally. The variability in treatment response to AD medications is influenced by genetic factors, sex, comorbidities, and medication history. Pharmacogenomics, the study of how an individual’s genetic makeup influences drug response, offers a promising approach to understanding these differences. This systematic review investigated the role of genetic polymorphisms in affecting treatment outcomes in AD. Following PRISMA guidelines, we systematically searched PubMed, Scopus, Cochrane, and PharmGKB databases for studies on AD, pharmacogenomics, and treatment response. Ten researchers independently screened the articles, with two independent reviewers resolving conflicts. A total of 1126 records were identified, and after removing duplicates and screening, 58 studies met inclusion criteria. APOE emerged as the most consistently studied gene, with ε2 and ε3 alleles generally associated with better responses to acetylcholinesterase inhibitors (AChEIs) and NMDA receptor antagonists, while ε4 carriage predicted poorer outcomes. The CYP2D610 allele, common in East Asian populations, was linked to enhanced donepezil response due to slower drug metabolism. Other genes, including ABCA1, A2M, CHRNA7, CHRFAM7A, and CHAT, showed potential associations with treatment response, particularly with AChEIs, though results varied across populations and study designs. Polymorphisms in inflammatory, metabolic, and vascular genes such as IL6, IDE, and ACE were also associated with cognitive outcomes, but findings were largely exploratory. In conclusion, APOE and CYP2D6 remain the most promising pharmacogenetic markers in AD, particularly for guiding donepezil therapy. However, evidence remains inconsistent due to varying study designs, populations, and clinical metrics. Additional genes show potential but require further validation. Larger, multiethnic studies with standardized treatment protocols and outcomes are needed to establish the clinical utility of pharmacogenomics in AD therapy.
Molecular mechanisms underlying the co-pathogenesis of abdominal aortic aneurysm and rheumatoid arthritis: evidence based on bioinformatics analysis and clinical data.
Wang Y, Zhang L, Jiang W … +2 more , Kuang Q, Qin X
BMC Med Genomics · 2025 Oct · PMID 41068798 · Full text
BACKGROUND: The incidence of abdominal aortic aneurysm (AAA) has been reported to be associated with rheumatoid arthritis (RA). This research aimed to analyze the co-pathogenesis of AAA and RA through bioinformatics and...
BACKGROUND: The incidence of abdominal aortic aneurysm (AAA) has been reported to be associated with rheumatoid arthritis (RA). This research aimed to analyze the co-pathogenesis of AAA and RA through bioinformatics and clinical data. METHODS: Microarray and single-cell RNA sequencing (scRNA-seq) datasets for AAA and RA were obtained from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified using R software (v4.2.2), followed by enrichment analyses. Hub genes were identified via the STRING database and Cytoscape software (v3.10.1). An immune cell infiltration analysis was conducted to identify key immune cell types associated with AAA and RA. Hub genes and key immune cell types were further validated using scRNA-seq datasets. NetworkAnalyst and the Drug Signature Database (DSigDB) were employed to explore the associations of hub genes with related diseases, miRNAs, transcription factors (TFs), drugs, and drug targets. Additionally, peripheral blood samples from 629 clinical patients were collected to validate the results of the immune cell infiltration analysis. RESULTS: The AAA and RA dataset revealed 61 common DEGs, including 20 upregulated and 41 downregulated genes. Three hub genes were screened from the common DEGs, and ITK was validated as hub gene in both AAA and RA datasets. Immune infiltration analysis revealed significant upregulation of monocytes in both AAA and RA, positively correlated with ITK expression. This was validated by scRNA-seq datasets confirming elevated ITK levels in monocytes. A total of eighteen related diseases, ten target miRNAs, eight TFs, and the top ten drugs and drug targets associated with ITK were identified. Analysis of clinical data revealed that monocyte levels were significantly elevated in patients with AAA and RA. CONCLUSIONS: Our study suggests that ITK may serve as a potential biomarker involved in the co-pathogenesis of AAA and RA. Moreover, monocytes appear to play an important role in this process. The regulatory network constructed for ITK may offer preliminary insights for future research.
Alcohol exposure significantly influences gene expression in the hypothalamus, highlighting complex links with gonadotropin-releasing hormone signaling and thyroid hormone production in adolescent mice.
Sun G, Peng Y, Hu C … +4 more , Zheng Y, Cheng Y, Qi X, Jin Y
BMC Med Genomics · 2025 Oct · PMID 41057899 · Full text
OBJECTIVE: Hypothalamic dysfunction occurs in alcohol use disorder (AUD). Here, we investigated the effects of alcohol exposure on hypothalamic gene expression in mice, and examined the role of the hypothalamus in AUD pa...
OBJECTIVE: Hypothalamic dysfunction occurs in alcohol use disorder (AUD). Here, we investigated the effects of alcohol exposure on hypothalamic gene expression in mice, and examined the role of the hypothalamus in AUD pathogenesis. METHODS: An alcohol exposure model was constructed in male C57BL/6 mice using the two-bottle drinking method. Transcriptome sequencing was used to analyze differential gene expression in the hypothalamus of alcohol exposure model and control mice. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of the differentially expressed genes were performed. In addition, real-time quantitative PCR was used to verify the differential expression of genes. RESULTS: We identified 225 differentially expressed genes by transcriptome sequencing, of which 64 showed increased expression and 161 decreased expression. GO enrichment analysis showed highest enrichment for developmental process terms. KEGG enrichment analysis showed highest enrichment for the gonadotropin-releasing hormone (GnRH) signaling pathway. PCR validation showed reduced expression of Prkcd, Ptk2b, and Adcy1 in the alcohol group compared with the control group, consistent with the sequencing results. The thyroid hormone synthesis pathway was significantly enriched, and PCR results showed that expression of Adcy1, Gpx2, and Ttr were decreased in the alcohol group compared with the control group, which was consistent with the sequencing results. CONCLUSION: Alcohol exposure in mice modulates the expression of genes associated with hypothalamic GnRH signaling pathway and thyroid hormone synthesis pathway. Expression of GnRH signaling pathway genes, Prkcd and Ptk2b, and of thyroid hormone synthesis pathway genes, Gpx2, Ttr, and Adcy1, was decreased. Our findings indicate that alcohol exposure is associated with altered expression of these genes, which may be relevant to the pathophysiology of AUD.
Overexpression of CCK Neuropeptide in brain is linked to ZBTB20 mutations: potential diagnostic relevance in glioblastoma.
Dakal TC, Sharma NK, Yadav V … +5 more , Kumar A, Chen P, Schmidt-Wolf I, Maciaczyk J, Sharma A
BMC Med Genomics · 2025 Oct · PMID 41057875 · Full text
Glioblastoma (GBM), the most malignant central nervous system cancer, has a median survival rate of 14–16 months. GBM patients have a poor prognosis despite rigorous multi-modal treatments like surgical resection, chemot...
Glioblastoma (GBM), the most malignant central nervous system cancer, has a median survival rate of 14–16 months. GBM patients have a poor prognosis despite rigorous multi-modal treatments like surgical resection, chemotherapy, and radiation. A systematic bioinformatics analysis of GXA gene expression datasets showed thirty-three overexpressed genes in GBM that were enriched in neuroactive ligand receptor interaction. Subsequently, bulk brain tissue gene expression profiling showed high to moderate expression of CCK, VGF, APLN, CNR1, GRIA4, and PDYN in the cortex, frontal cortex-BA9, BA24 region, cerebellar hemisphere, cerebellum, hippocampus, amygdala, basal ganglia, hypothalamus, substantia nigra, and spinal cord. Interesting, the cortex, frontal cortex-BA9, and BA24 regions had unbelievably high CCK expression. Brain cortex and frontal lobe mutational scoring showed significant rates of IDH1 (49%), TERT (25%), SETD2 (17%), and BRAF (9%). We initially confirmed glioblastoma (GBM) malignancy and therapeutic responses to CCK overexpression and IDH1 mutations in cerebral cortex and frontal cortex tissue samples. However, Mann–Whitney analysis revealed ZBTB20 mutations cause CCK expression, not IDH1 mutations. Overall, CCK expression and ZBTB20 mutations may be used in therapeutic treatments as predictive and diagnostic markers. The expression of CCK was not linked with overall survival and excludes its potential application as prognostic biomarker for GBM. This study showed that CCK and ZBTB20 based predictive and diagnostic technologies can improve precision and personalization of targeted cancer therapies for GBM patients. Nevertheless, experimental evidences have yet to reveal additional therapeutically meaningful connections between CCK expression and ZBTB20 mutations.
Association of CYP3A5 rs15524 and CYP3A7 rs776744 polymorphisms on tac IPV and clinical outcomes in early post-heart transplantation.
Chai Y, Hu L, Zhu Y … +5 more , Quan D, Li Y, Wang X, Yang Y, Wang Z
BMC Med Genomics · 2025 Oct · PMID 41057866 · Full text
BACKGROUND: The intrapatient variability (IPV) of tacrolimus (Tac) has gradually become a new index for the prognosis of organ transplantation. The gene polymorphism is involved in the pharmacokinetic process of Tac. The...
BACKGROUND: The intrapatient variability (IPV) of tacrolimus (Tac) has gradually become a new index for the prognosis of organ transplantation. The gene polymorphism is involved in the pharmacokinetic process of Tac. The aim of this study was to investigate the effects of genetic polymorphisms on Tac IPV and other clinical outcomes in heart transplant recipients during the early post-transplantation period. METHODS: Our study retrospectively collected the clinical data and genotyping results of 48 heart transplant recipients. SPSS (21.0) and Graphpad Prism (8.0) were used to analyze the effect of gene polymorphism on Tac concentration (C) and clinical outcome. RESULTS: The CYP3A5 rs15524 AA genotype has a higher trough concentrations/dose (C/D) value than G allele carriers, and CYP3A7 rs776744 CC genotype has a higher C/D value than T allele carriers. Patients with The CYP3A5 rs15524 and CYP3A7 rs776744 mutants had a higher IPV. One year after heart transplantation, the mortality of wild-type and mutant CYP3A5 rs15524 patients due to rejection was 0 vs. 10.7% (P = 0.255). The mortality caused by rejection in wild-type patients and mutant patients of CYP3A7 rs776744 was 4.5% vs. 7.7% (p = 0.564). CONCLUSIONS: Genetic polymorphisms of CYP3A5 rs15524 and CYP3A7 rs776744 affect tacrolimus metabolism in heart transplant recipients, significantly affecting Tac C/D during the early postoperative period. In addition, gene polymorphism may be related to Tac IPV and clinical outcome in patients with early heart transplantation.
CASC15 participated in the damage of vascular endothelial cells in atherosclerosis through interaction with miR-940.
Li T, Yang Z, Zhang K … +5 more , Song W, Liu B, Xiao S, Guo M, Li M
BMC Med Genomics · 2025 Oct · PMID 41057849 · Full text
BACKGROUND: This study aimed to explore the role of long non-coding RNA cancer Susceptibility 15 (CASC15) and microRNA (miR)-940 in atherosclerosis (AS) and to elucidate their potential mechanisms of action using an in v...
BACKGROUND: This study aimed to explore the role of long non-coding RNA cancer Susceptibility 15 (CASC15) and microRNA (miR)-940 in atherosclerosis (AS) and to elucidate their potential mechanisms of action using an in vitro cell model of AS. METHODS: Human umbilical vein endothelial cells (HUVECs) were subjected to oxidized low-density lipoproteins (ox-LDL) induction to establish an atherosclerotic cell model, and the expression levels of CASC15 and miR-940 in this model were evaluated. Cell viability and apoptosis were detected using the Cell Count Kit (CCK)-8 assay and flow cytometry, respectively. Quantitative real-time PCR was employed to quantify gene expression levels of CASC15, miR-940, and cell adhesion molecules intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1, while Enzyme-linked immunosorbent assay was used to measure the protein levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. Bioinformatics analysis was utilized to explore the target genes of miR-940 and their functional implications. RESULTS: The expression of CASC15 and miR-940 in ox-LDL-induced HUVECs showed an increase in CASC15 and a decrease in miR-940. Notably, miR-940 is a downstream target gene of CASC15. CASC15 knockdown mitigated ox-LDL-induced autophagy flux impairment, thereby promoting autophagy, whereas decreased levels of miR-940 significantly inhibit autophagy. Inhibition of CASC15 alleviates endothelial dysfunction caused by ox-LDL primarily through promoting activity and reducing apoptosis and inflammation. Conversely, a decrease in miR-940 exacerbates endothelial dysfunction. The addition of an autophagy activator relieved endothelial dysfunction, highlighting the involvement of the CASC15/miR-940 axis in regulating autophagy, and its role in modulating endothelial function impairment through autophagy regulation. CONCLUSION: Inhibition of CASC15 alleviates ox-LDL-induced endothelial dysfunction, potentially through the activation of autophagy via the modulation of miR-940.
Wiedemann-Steiner syndrome: description of genetic profiles and clinical phenotypes of 10 Korean pediatric patients.
Yoo J, Park AY, Ko JM
BMC Med Genomics · 2025 Oct · PMID 41053724 · Full text
BACKGROUND: Wiedemann-Steiner syndrome (WSS) is a genetic malformation syndrome caused by abnormalities in KMT2A. It is characterized by developmental delays, facial dysmorphism, hypertrichosis, failure to thrive, and mu...
BACKGROUND: Wiedemann-Steiner syndrome (WSS) is a genetic malformation syndrome caused by abnormalities in KMT2A. It is characterized by developmental delays, facial dysmorphism, hypertrichosis, failure to thrive, and musculoskeletal anomalies. Expanded applications of exome sequencing have increased the number of confirmed cases, broadening our understanding of the WSS spectrum. METHODS: We collected and organized the clinical and molecular features of 10 unrelated Korean patients diagnosed with WSS using molecular analysis. Clinical characteristics were presented based on the electronic medical records of the patients' regular visits. RESULTS: Subject patients consisted of four male and six female patients. The median patient age at diagnosis was 6.76 years. In most cases, the chief complaint upon visiting a clinician was developmental delay (8/10). The most frequently observed phenotypes included failure to thrive (9/10), short stature (7/10), developmental delay (10/10), and hypertrichosis (10/10). The degree of developmental delay varied among the patients. The majority (9/10) were diagnosed by exome sequencing, with the exception of one patient (1/10) who had a microdeletion at 11q23.3, encompassing partial KMT2A, as diagnosed by chromosomal microarray. All patients had private pathogenic or Likely pathogenic variants without any recurrent variants, and nine of the 10 variants were novel. CONCLUSIONS: Most Korean patients with WSS exhibited suggestive features, but most were not pathognomonic of WSS; thus, many patients may only be identifiable by molecular analyses. Phenotypes frequently overlap with other chromatinopathy syndromes. Future studies are needed to determine the genetic background of patients with molecularly unresolved WSS and to further delineate WSS.
An ADR pharmaceutical care for severe gastrointestinal bleeding of rivaroxaban in a patient with nonvalvular atrial fibrillation based on TDM and genetic testing: a case report.
Huang Y, Gao H, Chen M … +3 more , Lin Y, Liu H, Chen M
BMC Med Genomics · 2025 Oct · PMID 41044786 · Full text
BACKGROUND: Due to its predictable pharmacodynamics and pharmacokinetics, stable blood concentration, and relatively short half-life, rivaroxaban is widely used in the prevention and treatment of thrombosis. It neverthel...
BACKGROUND: Due to its predictable pharmacodynamics and pharmacokinetics, stable blood concentration, and relatively short half-life, rivaroxaban is widely used in the prevention and treatment of thrombosis. It nevertheless exhibits a certain level of inter-individual variability, and its safety concerns, including bleeding, are also becoming more noteworthy. CASE PRESENTATION: This paper describes an elderly patient with nonvalvular atrial fibrillation that was complicated with coronary heart disease, who is a homozygous mutation carrier of the ABCB1 allele (rs1045642 C > T, rs1128503 C > T, rs2032582 G > T). He was developed severe gastrointestinal bleeding during administration of oral rivaroxaban combined with aspirin. We investigated the possible causes of the bleeding, and any potential correlation with the ABCB1 gene polymorphism, combined with antiplatelet drugs and anemia. CONCLUSION: In the treatment of patients with atrial fibrillation, doctors should pay close attention to drug interactions with antiplatelet agents in high-risk groups and closely monitor various examination indexes, including hemoglobin. In this case, bleeding might be potentially influenced by homozygous mutations in ABCB1, but more clinical data are needed to clarify the association between ABCB1 polymorphism and rivaroxaban pharmacokinetics and bleeding.
Bone marrow mesenchymal stem cell-derived exosomes attenuate hepatic stellate cell activation through miR-223-3p-mediated mitophagy.
Ma L, Weng W, Chen J … +3 more , Wu H, Liang J, Lu F
BMC Med Genomics · 2025 Oct · PMID 41044587 · Full text
BACKGROUND: Liver fibrosis is a common pathological process in chronic liver diseases and effective treatments are lacking. The activation of hepatic stellate cells (HSCs) is a critical step in the development of liver f...
BACKGROUND: Liver fibrosis is a common pathological process in chronic liver diseases and effective treatments are lacking. The activation of hepatic stellate cells (HSCs) is a critical step in the development of liver fibrosis. Our previous research confirmed that bone marrow mesenchymal stem cell-derived exosomes (BMSC-exosomes) could regulate the level of miR-223-3p to alleviate intrahepatic inflammation, but whether they contribute to the protection of the liver against fibrosis remains unknown. METHODS: In this study, the antifibrotic function of BMSC-exosomes was validated through cell experiments. JS-1 cells (murine HSC line) were used as activated cells to simulate liver fibrosis. TGF-β is a stimulating factor for JS-1 cell activation. BMSC-exosomes were isolated via ultracentrifugation. RESULTS: Our results demonstrated that BMSC-exosomes internalized by JS-1 cells attenuated TGF-β-induced HSC activation and promoted HSC apoptosis. Moreover, BMSC-exosomes significantly reversed the upregulation of miR-223-3p levels and mitophagy induced by TGF-β. Luciferase activity reporter analysis further verified that hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) was a downstream target of miR-223-3p. By transfecting a miR-223-3p inhibitor, we found that downregulating miR-223-3p could increase the expression level of HMGCS1 and alleviate mitophagy, thereby reducing TGF-β-induced HSC activation and promoting HSC apoptosis. CONCLUSIONS: These results suggest that BMSC-exosomes may have antifibrotic effects. The mechanism may be related to regulating miR-223-3p in HSCs to target HMGCS1 and mitophagy.
Mono-allelic MUTYH mutation as the likely inherited etiology of hereditary breast cancer in a patient from a multi-cancer family- report of a family and literature review.
Sarmadi A, Javanmard SH, Zeinalian M … +2 more , Hosseinzadeh M, Tabatabaiefar MA
BMC Med Genomics · 2025 Oct · PMID 41035082 · Full text
BACKGROUND: Breast cancer (BC) is the most prevalent cancer globally. Carriers of pathogenic variants in high- or moderate-penetrance genes, have an increased risk of developing hereditary BC (HBC). While, MUTYH is known...
BACKGROUND: Breast cancer (BC) is the most prevalent cancer globally. Carriers of pathogenic variants in high- or moderate-penetrance genes, have an increased risk of developing hereditary BC (HBC). While, MUTYH is known to be associated with hereditary colonic polyposis and colorectal carcinoma, its role in BC is controversial. This study investigated the genetic cause of HBC in an Iranian family with a history of multiple cancer cases. METHODS: Clinical examination and exome sequencing (ES) was performed in a patient suffering from invasive ductal carcinoma from a family with several cases of different types of cancer. The pathogenicity of detected variants was done based on American Collage of Medical Genetics (ACMG) and Sanger sequencing was carried out for its validation. Furthermore, we performed a comprehensive review of the literature. RESULTS: Here, a pathogenic variant (p. A287Pfs*32) was identified in the MUTYH gene in mono-allelic status in four BC patients. However, this variant was previously reported as the cause of MutYH-associated polyposis (MAP) in homozygous status. The review of literature showed that the frequency of MUTYH mutation in BC patients population is in a range of 0.3-5.6%. CONCLUSION: In this study, a heterozygous pathogenic variant in the MUTYH gene was identified as the possible cause of BC in a multi-cancer family using ES. While the potential association between mono-allelic MUTYH mutations and an elevated risk of BC remains controversial, these findings highlight the necessity for a careful interpretation when assessing the role of MUTYH mutations in BC risk.
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