Human Gene最新文献

{"title":"A systems biology approach to uncover CNV-driven lncRNA regulatory networks in HPV-associated head and neck squamous cell carcinoma","authors":"Avantika Agrawal,&nbsp;Pubali Bhattacharjee,&nbsp;Swapnil Kumar,&nbsp;Vaibhav Vindal","doi":"10.1016/j.humgen.2025.201469","DOIUrl":"10.1016/j.humgen.2025.201469","url":null,"abstract":"<div><div>Copy number variations (CNVs) have been identified as critical contributors to head and neck squamous cell carcinoma (HNSCC) pathogenesis. Multi-omics analyses offer a comprehensive understanding of its underlying genetic complexities. Therefore, this study aims to examine the CNV-driven long non-coding RNAs (lncRNAs) influencing global regulatory triplet networks (lncRNA–miRNA–mRNA) in HPV-positive and HPV-negative HNSCC subtypes. Differential expression of miRNAs, mRNAs, and CNV-associated lncRNAs were identified using TCGA-HNSCC data. Subsequently, target prediction analyses enabled the construction of CNV-driven global triplet networks specific to HPV status. Gene Ontology (GO) analysis revealed that mRNAs in HPV-positive HNSCC were enriched in cancer-associated processes such as cell proliferation and extracellular matrix (ECM) organization. In contrast, those in HPV-negative HNSCC were primarily enriched in tissue remodeling, development, and cancer progression. KEGG pathway enrichment further supported these findings. The relationship between the CNV of lncRNA MCCC1-AS1 and its expression has revealed that there was no correlation between them in the HPV-positive HNSCC, while in the HPV-negative HNSCC, the gene expression of lncRNA MCCC1-AS1 was correlated with the CNV status. Survival analysis disclosed that the patient with a copy number gain of MCCC1-AS1 was associated with a shorter survival time, suggesting its potential as a prognostic biomarker. These findings highlight the significance of CNV-driven lncRNAs in the molecular landscape of HNSCC and suggest that MCCC1-AS1 may serve as a promising target for further investigation in diagnostic and therapeutic strategies.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201469"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144912332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Gγ-158C > T XmnI polymorphism with elevated HbF percentage in Sickle Cell Anemia patients: Evidence from a case-control study and meta-analysis","authors":"Satyabrata Meher ,&nbsp;Atanu Kumar Thakur ,&nbsp;Sushil Kumar Sahu ,&nbsp;Siris Patel ,&nbsp;Bimal Krushna Panda ,&nbsp;Kishalaya Das ,&nbsp;Snehadhini Dehury ,&nbsp;Sarmila Sahoo ,&nbsp;Mamata Pandey ,&nbsp;Bisnu Prasad Dash","doi":"10.1016/j.humgen.2025.201462","DOIUrl":"10.1016/j.humgen.2025.201462","url":null,"abstract":"<div><h3>Background</h3><div>Sickle Cell Anemia (SCA) is a monogenic disorder characterized by significant clinical heterogeneity, much of which is modulated by fetal hemoglobin (HbF) levels. The -158C &gt; T <em>Xmn</em>I polymorphism (rs7482144) in the Gγ-globin gene promoter is a known genetic determinant of HbF expression. This study investigates the association of the Gγ-158C &gt; T XmnI polymorphism with HbF levels in SCA patients from Eastern India and global evidence through a meta-analysis.</div></div><div><h3>Methods</h3><div>A case-control study was conducted involving 100 SCA patients and 50 healthy controls from Eastern India. Genotyping for the Gγ-158C &gt; T XmnI polymorphism was performed using PCR-RFLP. Clinical and hematological parameters, including HbF percentage, were assessed. Genotype and allele frequencies were compared between cases and controls. A meta-analysis was performed, incorporating 591 SCA cases and 531 controls were included from 10 published studies satisfying the criteria, including the present investigation, evaluating various genetic models (T vs C, TT vs CC, TT vs CC + CT, CT vs CC, TT + CT vs CC). Heterogeneity and publication bias were assessed using standard statistical methods.</div></div><div><h3>Results</h3><div>SCA patients exhibited significantly higher frequencies of the T allele (76.5 %) and TT genotype (66 %) compared to controls (T allele: 37 %, TT genotype: 22 %). HbF levels were significantly elevated in TT homozygotes (21.8 ± 8.57 %) compared to CT (17.5 ± 9.51 %) and CC (13.01 ± 5.35 %) genotypes (<em>p</em> &lt; 0.003). The T allele and TT genotype were strongly associated with SCA, with odds ratios (OR) of 0.18 (95 % CI: 0.11–0.30, <em>p</em> &lt; 0.0001) and 0.09 (95 % CI: 0.04–0.23, p &lt; 0.0001), respectively. Meta-analysis confirmed a significant association between the T allele and increased HbF levels in SCA across populations (T vs C: pooled OR = 0.359, 95 % CI: 0.200–0.643, <em>p</em> = 0.001; TT vs CC: pooled OR = 0.186, 95 % CI: 0.107–0.321, <em>p</em> = 0.000). Moderate heterogeneity was observed for some comparisons (I² up to 77.6 %), but no significant publication bias was detected.</div></div><div><h3>Conclusion</h3><div>The Gγ-158C &gt; T <em>Xmn</em>I polymorphism is significantly associated with increased HbF levels and a protective effect in SCA patients, both in the Eastern Indian population and globally. These findings highlight the importance of this genetic marker for prognostication and potential therapeutic targeting in SCA.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201462"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144831344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crosstalk between MitomiRs and cardiovascular disease","authors":"Rashi Khare,&nbsp;Nilanjana Ghosh,&nbsp;Sunanda Arya,&nbsp;Swati Srivastava,&nbsp;Iti Garg","doi":"10.1016/j.humgen.2025.201488","DOIUrl":"10.1016/j.humgen.2025.201488","url":null,"abstract":"<div><h3>Background</h3><div>Mitochondrial microRNAs (mitomiRs) have emerged as vital regulators in the etiology of cardiovascular disease (CVD). Differential mitomiR expression contributes to mitochondrial dysfunction which is a key contributor to heart failure, ischemia, and cardiomyopathic hypertrophy. Despite advances, the specific downstream pathways and molecular mechanisms influenced by mitomiRs remain inadequately defined. We have investigated mitomiRs which are associated with CVD.</div></div><div><h3>Methods</h3><div>A systematic literature review was conducted using PubMed to identify mitomiRs associated with cardiovascular disease. Experimentally validated target gene interactions were analyzed using MiRDB and MirTarBase. Protein-protein interaction (PPI) networks were constructed with STRING, and functional enrichment analyses, including Gene Ontology (GO) and KEGG pathway analyses, were performed using an SR plot. Hub gene identification was executed via the CytoHubba plugin in Cytoscape, pinpointing key regulatory nodes within the network.</div></div><div><h3>Results</h3><div>The present study identified 21 mitomiRs that modulate the coagulation gene pathway in cardiovascular disease. Notably, the amyloid precursor protein (APP) was recognized as a central hub. APP acts as a crucial intersection between the regulation of coagulation and mitochondrial protein clusters. Among the top 15 hub genes, APP was highlighted as a significant molecular regulator that potentially linked mitochondrial dysfunction with cardiovascular pathology.</div></div><div><h3>Conclusion</h3><div>Mitomir plays a critical role in the regulation of mitochondrial function in various cardiovascular diseases. Mitomir not only regulates the mitochondrial function but also are involved in the coagulation pathway. Mitochondrial dysfunction may have been a result of the involvement of amyloid precursor protein which itself is the main regulator of Alzheimer's disease. Hence uncovering the potential role behind APP in cardiovascular disease may help to unlock a potential target that is still missing in CVD.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201488"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145265457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utilizing explainable AI to decipher transcriptomic alterations in pancreatic cancer","authors":"Ankur Datta ,&nbsp;Esther Graceia Precious A ,&nbsp;Akshata Shetty ,&nbsp;Sridhar Raj S ,&nbsp;George Priya Doss C","doi":"10.1016/j.humgen.2025.201494","DOIUrl":"10.1016/j.humgen.2025.201494","url":null,"abstract":"<div><div>Diagnosing Pancreatic Cancer (PC) remains a formidable challenge for both clinicians and biomedical researchers due to its complex pathophysiology and late-stage detection. Although numerous investigations have elucidated key molecular pathways implicated in PC progression, this study advances the diagnostic paradigm by leveraging integrative transcriptomic analysis through sophisticated machine learning (ML) methodologies, notably LASSO regression and XGBoost. The closed-box characteristic of the XGBoost ML algorithm was resolved using the eXplainable artificial intelligence (XAI) based SHAP architecture. Data concerning gene expression profiles, mapped via microarray assays, from multiple datasets were retrieved and processed. A high-dimensional dataframe comprising 18,156 gene features for 464 patients was subjected to dimensionality reduction via LASSO regression to identify significant gene(s). The expression profiles of the 281 genes identified by LASSO were used to train the XGBoost disease classifier model, with an 80:20 train: test ratio. Conducting a 10-fold cross-validation yielded an average accuracy of 85 % for the XGBoost ML model. The SHAP framework highlighted the top gene features contributing to the decision-making of the XGBoost disease classifier model. The LASSO identified gene features were then biologically annotated to unravel the underlying mechanisms associated with PC disease. The proposed workflow, implemented in the current study, aims to enhance the existing landscape of PC diagnosis, reduce the rate of false positives typically observed with microarray-based techniques, and provide a strong foundation for computational studies with promising aspects for future cancer diagnostics and therapeutics.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201494"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polycystic ovary syndrome and the circadian clock: Understanding the link between metabolism, hormones, and sleep","authors":"Chaitanya Sree Somala ,&nbsp;Thirunavukarasou Anand ,&nbsp;Konda Mani Saravanan ,&nbsp;Damal Chandrasekar Mathangi","doi":"10.1016/j.humgen.2025.201497","DOIUrl":"10.1016/j.humgen.2025.201497","url":null,"abstract":"<div><div>Polycystic Ovary Syndrome (PCOS) is a complex endocrine disorder with significant metabolic, reproductive, and psychological effects. Emerging research indicates that the disruption of circadian rhythm significantly contributes to the onset and progression of PCOS, a feature that has been insufficiently addressed. This paper presents a distinctive and comprehensive exploration of how circadian discordance, through clock gene dysregulation, sleep-wake disturbances, and external factors such as shift work, contributes to the pathophysiology of the polygenic disorder known as PCOS. This review is distinctive in that it offers opportunities to synthesize knowledge in the molecular biology of insulin processes, endocrinology, and behavioral sciences concerning circadian rhythms, insulin sensitivity, glucose metabolism, regulation of reproductive hormones, and mental health outcomes, in contrast to the prior literature. The article is organized into sections that address the molecular basis of circadian imbalance, its impact on the hypothalamic-pituitary-ovarian (HPO) axis, and its psychological implications, including persistent mood disorders and cognitive impairments. Furthermore, it introduces the novel potential of chronotherapy and circadian-based lifestyle modifications as systemic therapeutic alternatives. This review advances the understanding of circadian biology in PCOS by integrating a multidisciplinary body of knowledge, addressing research gaps, and proposing a new avenue of investigation into therapeutic strategies focused on circadian alignment to improve patient outcomes in PCOS.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201497"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145362203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selected SNPs in the BDNF and DRD2 genes and their associations with antipsychotic-induced weight gain in a Sri Lankan cohort","authors":"Kajan Muneeswaran ,&nbsp;Varuni A. de Silva ,&nbsp;Madhubhashinee Dayabandara ,&nbsp;Raveen Hanwella ,&nbsp;Naduviladath Vishvanath Chandrasekharan","doi":"10.1016/j.humgen.2025.201464","DOIUrl":"10.1016/j.humgen.2025.201464","url":null,"abstract":"<div><div>Antipsychotic-induced weight gain (AIWG) is a prevalent and clinically significant side effect that compromises treatment adherence and exacerbates metabolic health risks in individuals receiving antipsychotic medication. While several genetic variants have been implicated in modulating AIWG risk, their population-specific pharmacogenetic architecture remains underexplored in South Asian settings. This study investigated the associations of four SNPs from two genes, rs6265 (<em>BDNF</em> gene), rs1799732, rs1800497, and rs4436578 (<em>DRD2</em> gene), with AIWG in a Sri Lankan schizophrenia cohort (<em>n</em> = 304). SNPs were genotyped via competitive amplification of differentially melting amplicons (CADMA) with high-resolution melt analysis (HRMA) and validated via the MassARRAY System. Statistical analyses, including association, and interaction analyses, were performed using the SNPstats online tool. Genotyping and association analyses revealed marginal association of rs6265 (T allele) with weight gain (OR = 3.25, 95 % CI: 0.85–12.51, <em>p</em> = 0.068), while a protective role for the A allele of rs1800497 was also identified (OR = 0.58, 95 % CI: 0.36–0.91, <em>p</em> = 0.018). This study highlights the utility of integrating genetic screening into psychiatric care to guide personalized treatment strategies and mitigate adverse drug effects in underrepresented populations.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201464"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144860303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment of the PCR inhibitory effect of the hair dye constituents and its role in forensic DNA analysis","authors":"Hirak Ranjan Dash ,&nbsp;Vaishnavi Gupta ,&nbsp;Dnyaneshwar Tanpure ,&nbsp;Braja Kishore Mohapatra","doi":"10.1016/j.humgen.2025.201471","DOIUrl":"10.1016/j.humgen.2025.201471","url":null,"abstract":"<div><div>Hair is among the most frequent types of biological evidence recovered at crime scenes, playing a crucial role in identifying culprits. Often, the recovered hair samples are dyed with various routinely used hair dyes. A survey of 182 individuals showed that the majority (82 %) of individuals dye their hair frequently, at least once a month. Cetearyl alcohol, propylene glycol, and disodium EDTA are the most common ingredients of the commercially available hair dyes. <em>In-silico</em> analysis predicted that the citric acid component of hair dye has the strongest affinity with Taq Polymerase (−6.1 Kcal/mol), followed by ascorbic acid (−5.5 Kcal/mol), resorcinol (−5.0 Kcal/mol), trisodium EDTA (−4.8 Kcal/mol), phosphoric acid (−4.0 Kcal/mol), glycerin and cetyl alcohol (−3.7 Kcal/mol), propylene glycol (−3.5 Kcal/mol), ethanolamine (−3.0 Kcal/mol) and hydrogen peroxide (−2.9 Kcal/mol). Molecular docking studies further revealed that the residues of arginine, threonine, glutamine, lysine, threonine, asparagine, serine, aspartic acid, phenylalanine, leucine, methionine, and tryptophan are the responsible motifs of Taq Polymerase which bind with different hair dye chemical constituents. In a singleplex PCR, the <em>CYCLO</em> gene was amplified only in the presence of cetyl alcohol, glycerin, and ethanolamine. All 23 STR markers were amplified using the Fusion 6C kit in the presence of hair dyes. However, the dye constituents adversely affected the Locus Balance of the STR profiles. Thus, most of the hair dye components act as potential PCR inhibitors by interacting with Taq Polymerase and suitable mitigation strategies should be employed for such forensic biological samples.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201471"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144917761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered expression patterns of lncRNA MEG3 and LINC01611 in patients with colorectal cancer","authors":"Niloofar Faraji ,&nbsp;Mohammad Almasi ,&nbsp;Majid Mirmazloumi ,&nbsp;Nasim Padasht ,&nbsp;Sahand Sadat Mansouri ,&nbsp;Fatemeh Ghaderibarmi ,&nbsp;Haniyeh Royatpour ,&nbsp;Fatemeh Modaresi ,&nbsp;Kourosh Kazempour Samak ,&nbsp;Fahimeh Abedini Bajgiran ,&nbsp;Tahereh Zeinali ,&nbsp;Narges Eslami ,&nbsp;Dariush Shanehbandi ,&nbsp;Ali Salehzadeh","doi":"10.1016/j.humgen.2025.201470","DOIUrl":"10.1016/j.humgen.2025.201470","url":null,"abstract":"<div><div>Colorectal cancer (CRC) is a major global health challenge, with long non-coding RNAs (lncRNAs) gaining attention as potential diagnostic biomarkers. This study aimed to experimentally validate bioinformatics findings on the expression patterns of maternally expressed gene 3 (MEG3) and LINC01611 in CRC patients from a specific ethnic population while considering associated risk factors. This in vitro study initially recruited 50 patients from a single ethnic group, with 48 completing the analysis after the exclusion of two samples. Two lncRNAs, MEG3 and LINC01611, were selected using Gene Expression Omnibus (GEO) microarray data and identified via R/BioConductor. Paired tissue samples (tumor and adjacent margins) were collected during surgery, and RNAs were extracted. Demographic and clinical data of patients were recorded, and gene expression was analyzed using quantitative real-time PCR (qPCR), with GAPDH as the internal control. Data analysis was performed using GraphPad Prism and SPSS software, with the significance level set at <em>P</em> &lt; 0.05. The mean age of the patients was 59.5 ± 3.53 years, with 58.3 % (<em>n</em> = 28) being male, and 37.5 % of the patients had a history of smoking. The majority of patients had poorly differentiated (41.7 %) and stage II tumor (43.8 %), with lymph node metastasis commonly observed (60.4 %). The Wilcoxon signed-rank test revealed significant downregulation of MEG3 (32.396 fold change)and LINC01611(38.923 fold change) in tumor tissues compared to adjacent margins. A family history of CRC was associated with higher expression levels of MEG3 (1.48-fold, <em>P</em> = 0.038) and LINC01611 (1.03-fold, <em>P</em> = 0.007) in both tumor and margin tissues. Multivariable regression analysis demonstrated that lncRNAs had a significant association with tumor differentiation (<em>P</em> &lt; 0.05), while other variables showed no statistically significant association (<em>P</em> &gt; 0.05). Also, positive correlations were observed between MEG3 and LINC01611 expression levels in tumor (<em>r</em> = 0.649, <em>P</em> &lt; 0.001) and margin (<em>r</em> = 0.424, <em>P</em> = 0.003) tissues. The significant downregulation of MEG3 and LINC01611 in tumor tissues compared to adjacent margin tissues highlights their potential role as tumor suppressors in CRC. These findings support further investigation into these lncRNAs as diagnostic biomarkers.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201470"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144931728","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The interplay between IL-18 rs1946518 polymorphism, TSH dysregulation, and vitamin D3 deficiency in Hashimoto's thyroiditis","authors":"Noor Al-Huda Saber Sadiq,&nbsp;Dhifaf Zeki Aziz","doi":"10.1016/j.humgen.2025.201465","DOIUrl":"10.1016/j.humgen.2025.201465","url":null,"abstract":"<div><h3>Background</h3><div>Hashimoto's thyroiditis (HT) is an autoimmune thyroid disorder shaped by both genetic predisposition and environmental influences. One gene of growing interest is interleukin-18 (IL-18), particularly its rs1946518 (T/G) promoter polymorphism, which may affect inflammatory responses. Meanwhile, vitamin D3 has emerged as a key immunomodulatory factor, yet its interaction with genetic markers in HT remains unclear.</div></div><div><h3>Objective</h3><div>The primary objective of this study was to examine the potential role of the IL-18 gene promoter polymorphism (rs1946518, T/G) in the development of Hashimoto's thyroiditis (HT) among Iraqi patients. The investigation focused on whether this genetic variation affects serum IL-18 levels and contributes to immune and endocrine disturbances commonly observed in HT, including altered levels of thyroid-stimulating hormone (TSH), vitamin D3, and thyroid-specific autoantibodies (anti-TPO and anti-Tg). To further explore the functional implications of IL-18 in the disease process, molecular docking analysis was conducted to evaluate the potential interaction between IL-18 and active vitamin D3 [1,25(OH)₂D₃], aiming to examine the potential molecular interaction how vitamin D may modulate inflammatory responses in HT.</div></div><div><h3>Methods</h3><div>A total of 100 participants were included in a case-control design: 60 patients with HT and 40 matched health controls. Genotyping for rs1946518 was performed using Tetra-ARMS PCR. Serum levels of IL-18, 25(OH)D₃, TSH, anti-TPO, and anti-Tg were measured. Statistical comparisons and molecular docking analyses were conducted to understand both genetic and biochemical patterns.</div></div><div><h3>Results</h3><div>Carriers of the G allele showed significantly higher IL-18 levels, elevated TSH and autoantibodies, and lower vitamin D3 compared to TT/TG genotypes. Newly diagnosed patients had the highest IL-18 and lowest vitamin D3 concentrations. Molecular docking indicated a stable interaction between IL-18 and 1,25(OH)₂D₃, suggesting vitamin D might directly influence IL-18 function.</div></div><div><h3>Conclusion</h3><div>The <em>IL-18</em> rs1946518 G allele may predispose individuals to stronger inflammatory activity in HT, while concurrent vitamin D3 deficiency could amplify this response.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201465"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144867063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimating drivers of breast tissue transitions from normal to tumor state","authors":"Swapnil Kumar,&nbsp;Vaibhav Vindal","doi":"10.1016/j.humgen.2025.201506","DOIUrl":"10.1016/j.humgen.2025.201506","url":null,"abstract":"<div><div>Tumor tissues are characterized by dysregulated gene expression patterns leading to altered cellular pathways and molecular functions as a result of their transition from normal to tumor state. Further, tumor-adjacent normal tissues (TANTs), utilized as a control in cancer research, are not molecularly normal and differ from healthy normal tissues. These TANTs represent a distinctive transitional state between normal and tumor states. However, the mechanism underlying this state transition, expression dysregulation, and perturbed regulation remain largely unexplored and elusive. Herein, the transitions of breast tissues from normal and TANT to tumor states were modeled using gene expression and regulation data to estimate key drivers underlying these transitions. As a result, we identified 645 shared driver genes underlying the transitions of breast tissues from the healthy normal state to the adjacent normal and tumor states. Besides, we identified 635 shared driver genes underlying the transitions of TANTs to different subtypes. When we intersected both lists of shared driver genes, 615 commonly shared driver genes across the state transitions were observed. Subsequently, functional annotations of these driver genes revealed their involvement in cell growth and maintenance-related activity. Additionally, key pathways associated with cancer pathogenesis, such as Wnt signaling, Notch signaling, NF-kappa B signaling, and PD-L1 expression and PD-1 checkpoint pathway in cancer, were found significantly enriched with these shared driver genes. Thus, the shared driver genes identified across tissue transitions provide ways forward to devise more efficient diagnostic and therapeutic strategies for early and effective disease management.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201506"},"PeriodicalIF":0.7,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465897","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}