Pub Date : 2025-10-29DOI: 10.1016/j.humgen.2025.201504
Chenxi Liu , Wen Wen , Zheng Zhang
This study reports a familial hypertrophic cardiomyopathy (HCM) case caused by the MYH6 c.5467G > T (p. Glu1823Ter) nonsense variant. The proband, a 44-year-old male, presented with sudden-onset chest pain and dyspnea. Echocardiography revealed left atrial enlargement, asymmetric septal hypertrophy, and left ventricular outflow tract obstruction, while cardiac magnetic resonance imaging demonstrated mid-septal delayed enhancement, confirming HCM diagnosis. Genetic analyses via next-generation sequencing (NGS) and Sanger sequencing identified a heterozygous nonsense variant (c.5467G > T) in the MYH6 gene, predicted to induce nonsense-mediated mRNA decay (NMD). Three-generation pedigree analysis showed complete co-segregation of this variant with HCM phenotype. Mutation carriers exhibited varying degrees of HCM, whereas non-carriers had normal cardiac structures. These findings suggest the MYH6 c.5467G > T variant as a contributor to HCM development.
{"title":"Novel nonsense mutation in MYH6 gene identified as the cause of familial hypertrophic cardiomyopathy – A case report and literature review","authors":"Chenxi Liu , Wen Wen , Zheng Zhang","doi":"10.1016/j.humgen.2025.201504","DOIUrl":"10.1016/j.humgen.2025.201504","url":null,"abstract":"<div><div>This study reports a familial hypertrophic cardiomyopathy (HCM) case caused by the MYH6 c.5467G > T (p. Glu1823Ter) nonsense variant. The proband, a 44-year-old male, presented with sudden-onset chest pain and dyspnea. Echocardiography revealed left atrial enlargement, asymmetric septal hypertrophy, and left ventricular outflow tract obstruction, while cardiac magnetic resonance imaging demonstrated mid-septal delayed enhancement, confirming HCM diagnosis. Genetic analyses via next-generation sequencing (NGS) and Sanger sequencing identified a heterozygous nonsense variant (c.5467G > T) in the MYH6 gene, predicted to induce nonsense-mediated mRNA decay (NMD). Three-generation pedigree analysis showed complete co-segregation of this variant with HCM phenotype. Mutation carriers exhibited varying degrees of HCM, whereas non-carriers had normal cardiac structures. These findings suggest the MYH6 c.5467G > T variant as a contributor to HCM development.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201504"},"PeriodicalIF":0.7,"publicationDate":"2025-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465899","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}
Green synthesis is a preferred method for producing silver nanoparticles (Ag-NPs). In addition to its advantages for industrial and biomedical applications, it also represents a promising research field. This study aimed to evaluate the effects of chlorpyrifos (CPF) on thyroid hormone levels and the expression of inflammatory factors while highlighting the therapeutic potential of curcumin-synthesized silver nanoparticles (CUR-Ag-NPs) in mitigating CPF-induced thyroid damage.
Materials and methods
Six groups of rats were studied: control, CPF (5 mg/kg), CUR-AgNPs 40 μg/kg, CUR-AgNPs 80 μg/kg, CPF+ CUR-AgNPs 40, μg/kg, and CPF+ CUR-AgNPs 80 μg/kg. Treatments were administered daily for 30 days. At the end of the study, the rats were anesthetized with ketamine (50 mg/kg), and xylazine, (10 mg/kg). Blood was collected for serum analysis of thyroid hormone levels and thyroid gland tissue was preserved in RNAlater to the evaluation of inflammation markers.
Results
CPF exposure increased the expression of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and nitric oxide synthase 2 (NOS2). Co-administration of CUR-AgNPs significantly reduced the expression of these genes. CPF also disrupted thyroid hormone secretion, while CUR-AgNPs treatment in CPF-exposed rats nearly restored thyroid function.
Conclusion
These findings suggest that CUR-AgNPs can attenuate CPF-induced thyroid toxicity, offering potential therapeutic value.
{"title":"Curcumin-synthesized silver nanoparticles modulate inflammatory and thyroid-related gene expression in pubertal rats exposed to chlorpyrifos","authors":"Mohammad Hossein Gorji Dizabadi , Maryam Rezaei , Tahereh Farkhondeh , Saeed Samargahndian , Zahra Khademi , Atena Mansouri","doi":"10.1016/j.humgen.2025.201503","DOIUrl":"10.1016/j.humgen.2025.201503","url":null,"abstract":"<div><h3>Introduction</h3><div>Green synthesis is a preferred method for producing silver nanoparticles (Ag-NPs). In addition to its advantages for industrial and biomedical applications, it also represents a promising research field. This study aimed to evaluate the effects of chlorpyrifos (CPF) on thyroid hormone levels and the expression of inflammatory factors while highlighting the therapeutic potential of curcumin-synthesized silver nanoparticles (CUR-Ag-NPs) in mitigating CPF-induced thyroid damage.</div></div><div><h3>Materials and methods</h3><div>Six groups of rats were studied: control, CPF (5 mg/kg), CUR-AgNPs 40 μg/kg, CUR-AgNPs 80 μg/kg, CPF+ CUR-AgNPs 40, μg/kg, and CPF+ CUR-AgNPs 80 μg/kg. Treatments were administered daily for 30 days. At the end of the study, the rats were anesthetized with ketamine (50 mg/kg), and xylazine, (10 mg/kg). Blood was collected for serum analysis of thyroid hormone levels and thyroid gland tissue was preserved in RNAlater to the evaluation of inflammation markers.</div></div><div><h3>Results</h3><div>CPF exposure increased the expression of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and nitric oxide synthase 2 (NOS2). Co-administration of CUR-AgNPs significantly reduced the expression of these genes. CPF also disrupted thyroid hormone secretion, while CUR-AgNPs treatment in CPF-exposed rats nearly restored thyroid function.</div></div><div><h3>Conclusion</h3><div>These findings suggest that CUR-AgNPs can attenuate CPF-induced thyroid toxicity, offering potential therapeutic value.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201503"},"PeriodicalIF":0.7,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415608","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}
Diabetic foot ulcers (DFUs) are a prominent and serious outcome of diabetes that can have a major impact on quality of life. Diabetic foot ulcers (DFUs) exhibit a delayed recovery owing to the physiological healing cascade. The typical wound healing process, which encompasses angiogenesis, inflammation, and extracellular matrix (ECM) remodeling, is disrupted and inhibited in diabetic foot ulcers (DFUs). Upon injury to the tissue, neutrophils and monocytes migrate to the site of injury and secrete reactive oxygen species (ROS), matrix metalloproteinase (MMP)-8. In addition to that, the other biomarkers like procalcitonin, pentraxin-3, C-reactive protein (CRP), interleukins (ILs), and tumor necrosis factor-α (TNF-α), are secreted as an inflammatory response. These inflammatory mediators play a significant role as novel biomarkers reflecting the impact of therapeutic interventions. Numerous studies state that, single nucleotide variants (SNVs) in multiple genes may contribute to abnormal inflammatory response leading to the delayed healing of diabetic foot ulcers (DFUs). This article summarizes current information on the generation of diabetic foot ulcers (DFUs) concerning single-nucleotide variants (SNVs). This review unveils a comprehensive summary of emerging biomarkers and single-nucleotide variants (SNVs) that facilitate accurate diagnosis and risk assessment of diabetic foot ulcers (DFUs).
{"title":"Genetic and molecular insights into diabetic foot ulcers: Unveiling biomarkers for precision medicine","authors":"Ratanjeet Singh Sudan, Priyanka Garg, Palakurthi Yanadaiah","doi":"10.1016/j.humgen.2025.201500","DOIUrl":"10.1016/j.humgen.2025.201500","url":null,"abstract":"<div><div>Diabetic foot ulcers (DFUs) are a prominent and serious outcome of diabetes that can have a major impact on quality of life. Diabetic foot ulcers (DFUs) exhibit a delayed recovery owing to the physiological healing cascade. The typical wound healing process, which encompasses angiogenesis, inflammation, and extracellular matrix (ECM) remodeling, is disrupted and inhibited in diabetic foot ulcers (DFUs). Upon injury to the tissue, neutrophils and monocytes migrate to the site of injury and secrete reactive oxygen species (ROS), matrix metalloproteinase (MMP)-8. In addition to that, the other biomarkers like procalcitonin, pentraxin-3, C-reactive protein (CRP), interleukins (ILs), and tumor necrosis factor-α (TNF-α), are secreted as an inflammatory response. These inflammatory mediators play a significant role as novel biomarkers reflecting the impact of therapeutic interventions. Numerous studies state that, single nucleotide variants (SNVs) in multiple genes may contribute to abnormal inflammatory response leading to the delayed healing of diabetic foot ulcers (DFUs). This article summarizes current information on the generation of diabetic foot ulcers (DFUs) concerning single-nucleotide variants (SNVs). This review unveils a comprehensive summary of emerging biomarkers and single-nucleotide variants (SNVs) that facilitate accurate diagnosis and risk assessment of diabetic foot ulcers (DFUs).</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201500"},"PeriodicalIF":0.7,"publicationDate":"2025-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415619","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}
Pub Date : 2025-10-24DOI: 10.1016/j.humgen.2025.201499
Mina Kazemzadeh , Reza Safaralizadeh , Amir Ali Mokhtarzadeh , Mohammad Ali Hosseinpour Feizi
Background
The significance of long non-coding RNAs, a new class of regulatory RNAs, is progressively emerging in the initiation, progression, and invasion of cancers, including thyroid cancer. PURPL (LINC01021) is one of the novel lincRNAs that has just been identified in a few human cancers. Considering the inadequate comprehension of PURPL expression and its alteration in thyroid cancer, the primary objective of this study was to quantitatively assess PURPL expression in thyroid tissue and to explore its dysregulation in patients with thyroid cancer for the first time.
Materials and methods
The Cancer Genome Atlas database was utilized to evaluate the relative expression of PURPL across various cancer types. Subsequently, quantitative real-time PCR was employed to assess PURPL expression in paired tumor and adjacent tumor-free tissue samples obtained from 30 individuals with thyroid cancer. Bioinformatics analysis was then performed to identify co-expressed genes and associated pathways with PURPL. One of the identified co-expressed genes, MDM2, was further investigated for its correlation with PURPL expression through real-time PCR. Additionally, efforts were made to correlate PURPL expression with clinicopathological features of thyroid cancer.
Results
Real-time PCR analysis revealed the upregulation of PURPL during tumorigenesis in thyroid cancer. However, dysregulation of PURPL did not show a significant correlation with clinical characteristics. Bioinformatics analysis identified approximately 1000 genes correlated with PURPL expression, with MDM2 exhibiting the highest positive correlation. Experimental validation through real-time PCR confirmed a positive correlation between MDM2 and PURPL expression in thyroid cancer cells. Additionally, the oncogenic CASC19 and tumor suppressor TLE5 demonstrated strong positive and negative correlations with PURPL, respectively, suggesting a complex regulatory role in thyroid cancer progression.
Conclusion
The significant upregulation of PURPL in thyroid cancer, along with its positive correlation with oncogenes such as MDM2, underscores the potential role of PURPL in cancer-associated pathways.
{"title":"Understanding the dysregulation of PURPL, a novel long intergenic noncoding RNA, in thyroid cancer progression","authors":"Mina Kazemzadeh , Reza Safaralizadeh , Amir Ali Mokhtarzadeh , Mohammad Ali Hosseinpour Feizi","doi":"10.1016/j.humgen.2025.201499","DOIUrl":"10.1016/j.humgen.2025.201499","url":null,"abstract":"<div><h3>Background</h3><div>The significance of long non-coding RNAs, a new class of regulatory RNAs, is progressively emerging in the initiation, progression, and invasion of cancers, including thyroid cancer. PURPL (LINC01021) is one of the novel lincRNAs that has just been identified in a few human cancers. Considering the inadequate comprehension of PURPL expression and its alteration in thyroid cancer, the primary objective of this study was to quantitatively assess PURPL expression in thyroid tissue and to explore its dysregulation in patients with thyroid cancer for the first time.</div></div><div><h3>Materials and methods</h3><div>The Cancer Genome Atlas database was utilized to evaluate the relative expression of PURPL across various cancer types. Subsequently, quantitative real-time PCR was employed to assess PURPL expression in paired tumor and adjacent tumor-free tissue samples obtained from 30 individuals with thyroid cancer. Bioinformatics analysis was then performed to identify co-expressed genes and associated pathways with PURPL. One of the identified co-expressed genes, MDM2, was further investigated for its correlation with PURPL expression through real-time PCR. Additionally, efforts were made to correlate PURPL expression with clinicopathological features of thyroid cancer.</div></div><div><h3>Results</h3><div>Real-time PCR analysis revealed the upregulation of PURPL during tumorigenesis in thyroid cancer. However, dysregulation of PURPL did not show a significant correlation with clinical characteristics. Bioinformatics analysis identified approximately 1000 genes correlated with PURPL expression, with MDM2 exhibiting the highest positive correlation. Experimental validation through real-time PCR confirmed a positive correlation between MDM2 and PURPL expression in thyroid cancer cells. Additionally, the oncogenic CASC19 and tumor suppressor TLE5 demonstrated strong positive and negative correlations with PURPL, respectively, suggesting a complex regulatory role in thyroid cancer progression.</div></div><div><h3>Conclusion</h3><div>The significant upregulation of PURPL in thyroid cancer, along with its positive correlation with oncogenes such as MDM2, underscores the potential role of PURPL in cancer-associated pathways.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201499"},"PeriodicalIF":0.7,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145415609","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}
Pub Date : 2025-10-24DOI: 10.1016/j.humgen.2025.201498
Javad Omidi
MicroRNAs (miRNAs) are key regulators of post-transcriptional gene expression and have been increasingly implicated in the pathogenesis of rare malignancies such as adrenocortical carcinoma (ACC). Here, a systems biology approach was employed to construct and analyze context-specific competing endogenous RNA (ceRNA) networks using transcriptomic profiles from ACC tumors (TCGA) and normal adrenal tissues obtained from both GTEx 2025 and miRNATissueAtlas 2025 datasets, leveraging a novel integrative analytical framework specifically developed in this study. Comparative network topology revealed extensive regulatory rewiring in tumors, with miR-507 and miR-665 emerging as tumor-specific central miRNAs. While miR-507 was significantly upregulated and associated with favorable patient survival, miR-665 was downregulated and displayed radiation-sensitive expression dynamics. Target gene prediction and correlation analyses identified distinct sets of oncogenic and tumor-suppressive genes regulated by each miRNA. Functional enrichment and PPI network analysis indicated that miR-507 targets are strongly enriched in cell cycle, mitotic checkpoint, and chromosomal stability pathways, whereas miR-665 influences more context-dependent immune and signaling mechanisms. These findings support the prognostic and therapeutic potential of miR-507 in ACC and suggest a radiotherapy-modulated regulatory role for miR-665. This study demonstrates the power of multi-source transcriptomic integration for discovering functional miRNA hubs in rare endocrine cancers.
{"title":"miR-507 and miR-665 as central MicroRNA regulators in the ceRNA network of adrenocortical carcinoma: A systems biology approach","authors":"Javad Omidi","doi":"10.1016/j.humgen.2025.201498","DOIUrl":"10.1016/j.humgen.2025.201498","url":null,"abstract":"<div><div>MicroRNAs (miRNAs) are key regulators of post-transcriptional gene expression and have been increasingly implicated in the pathogenesis of rare malignancies such as adrenocortical carcinoma (ACC). Here, a systems biology approach was employed to construct and analyze context-specific competing endogenous RNA (ceRNA) networks using transcriptomic profiles from ACC tumors (TCGA) and normal adrenal tissues obtained from both GTEx 2025 and miRNATissueAtlas 2025 datasets, leveraging a novel integrative analytical framework specifically developed in this study. Comparative network topology revealed extensive regulatory rewiring in tumors, with miR-507 and miR-665 emerging as tumor-specific central miRNAs. While miR-507 was significantly upregulated and associated with favorable patient survival, miR-665 was downregulated and displayed radiation-sensitive expression dynamics. Target gene prediction and correlation analyses identified distinct sets of oncogenic and tumor-suppressive genes regulated by each miRNA. Functional enrichment and PPI network analysis indicated that miR-507 targets are strongly enriched in cell cycle, mitotic checkpoint, and chromosomal stability pathways, whereas miR-665 influences more context-dependent immune and signaling mechanisms. These findings support the prognostic and therapeutic potential of miR-507 in ACC and suggest a radiotherapy-modulated regulatory role for miR-665. This study demonstrates the power of multi-source transcriptomic integration for discovering functional miRNA hubs in rare endocrine cancers.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201498"},"PeriodicalIF":0.7,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145362204","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}
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.
{"title":"Polycystic ovary syndrome and the circadian clock: Understanding the link between metabolism, hormones, and sleep","authors":"Chaitanya Sree Somala , Thirunavukarasou Anand , Konda Mani Saravanan , 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":"2025-10-18","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}
Defining the etiology of multifactorial diseases, such as Parkinson's disease (PD), poses significant challenges in diagnosis, management, and treatment strategies. PD is characterized by progressive neurological degeneration. Current scientific evidence indicates that this condition arises from an intricate interplay of genetic and environmental factors. Notably, single nucleotide polymorphisms (SNPs) identified in various genes have been implicated in enhancing susceptibility to this disease. This study aims to investigate the association of two specific polymorphisms, IL-10 gene; −1087 G > A and mir146a gene; rs2910164 C > G, with the prevalence of PD.
Methods
This investigation employed a case-control design that included 96 participants in both the case and control groups. The identification of alleles was executed using the Tetra-primer Amplification Refractory Mutation System-Polymerase Chain Reaction (T-ARMS-PCR) method. Subsequent genetic and statistical analyses of the findings were performed utilizing POPGENE and SPSS software.
Result
The results indicated that the distribution of mir146a gene SNPs within the control and patient populations did not adhere to Hardy-Weinberg equilibrium. Specifically, the frequency of the G allele in patients diagnosed with PD was significantly lower than that observed in the control cohort. Furthermore, individuals carrying the GC genotype exhibited an elevated risk of developing PD, with p-values <0.05. Conversely, the distribution of IL-10 gene SNPs conformed to Hardy-Weinberg equilibrium within both groups, and no statistically significant association was found between IL-10 gene SNPs and the risk of PD.
Conclusion
The findings from this study suggest that the IL-10 gene −1087 G > A polymorphism does not contribute to increased susceptibility to PD within the studied population. Conversely, the mir146a gene rs2910164 C > G polymorphism appears to be associated with PD risk. Notably, the G allele of this SNP correlates with a decreased risk of the disease, while the GC genotype is linked to an increased likelihood of developing Parkinson's disease.
定义多因素疾病的病因，如帕金森病（PD），在诊断、管理和治疗策略方面提出了重大挑战。PD以进行性神经变性为特征。目前的科学证据表明，这种情况是由遗传和环境因素复杂的相互作用引起的。值得注意的是，在各种基因中发现的单核苷酸多态性（SNPs）与增加对这种疾病的易感性有关。本研究旨在探讨两种特定多态性的关联，IL-10基因；−1087 G >； A和mir146a基因；rs2910164 C >； G，与PD患病率相关。方法本研究采用病例-对照设计，病例组和对照组各96例。等位基因鉴定采用四引物扩增难突变系统-聚合酶链反应（T-ARMS-PCR）方法。随后使用POPGENE和SPSS软件对结果进行遗传和统计分析。结果mir146a基因snp在对照组和患者群体中的分布不符合Hardy-Weinberg平衡。具体来说，诊断为PD的患者中G等位基因的频率明显低于对照组。此外，携带GC基因型的个体患PD的风险增加，p值为<；0.05。相反，IL-10基因snp在两组内的分布符合Hardy-Weinberg平衡，IL-10基因snp与PD风险之间无统计学意义的关联。结论IL-10基因- 1087 G >； A多态性与研究人群PD易感性增加无关。相反，mir146a基因rs2910164 C >； G多态性似乎与PD风险相关。值得注意的是，该SNP的G等位基因与疾病风险降低相关，而GC基因型与患帕金森病的可能性增加相关。
{"title":"Exploring genetic associations in Parkinson's disease: The role of IL-10; −1087G>a and mir146a; rs2910164 C>G polymorphisms","authors":"Javid Ashtari Mahini , Zahra Shahbazi , Maryam Rahimi , Maryam Seyedolmohadesin","doi":"10.1016/j.humgen.2025.201493","DOIUrl":"10.1016/j.humgen.2025.201493","url":null,"abstract":"<div><h3>Introduction</h3><div>Defining the etiology of multifactorial diseases, such as Parkinson's disease (PD), poses significant challenges in diagnosis, management, and treatment strategies. PD is characterized by progressive neurological degeneration. Current scientific evidence indicates that this condition arises from an intricate interplay of genetic and environmental factors. Notably, single nucleotide polymorphisms (SNPs) identified in various genes have been implicated in enhancing susceptibility to this disease. This study aims to investigate the association of two specific polymorphisms, <em>IL-10</em> gene; −1087 G > A and <em>mir146a</em> gene<em>;</em> rs2910164 C > G, with the prevalence of PD.</div></div><div><h3>Methods</h3><div>This investigation employed a case-control design that included 96 participants in both the case and control groups. The identification of alleles was executed using the Tetra-primer Amplification Refractory Mutation System-Polymerase Chain Reaction (T-ARMS-PCR) method. Subsequent genetic and statistical analyses of the findings were performed utilizing POPGENE and SPSS software.</div></div><div><h3>Result</h3><div>The results indicated that the distribution of <em>mir146a</em> gene SNPs within the control and patient populations did not adhere to Hardy-Weinberg equilibrium. Specifically, the frequency of the G allele in patients diagnosed with PD was significantly lower than that observed in the control cohort. Furthermore, individuals carrying the GC genotype exhibited an elevated risk of developing PD, with <em>p</em>-values <0.05. Conversely, the distribution of <em>IL-10</em> gene SNPs conformed to Hardy-Weinberg equilibrium within both groups, and no statistically significant association was found between <em>IL-10</em> gene SNPs and the risk of PD.</div></div><div><h3>Conclusion</h3><div>The findings from this study suggest that the <em>IL-10</em> gene −1087 G > A polymorphism does not contribute to increased susceptibility to PD within the studied population. Conversely, the <em>mir146a</em> gene rs2910164 C > G polymorphism appears to be associated with PD risk. Notably, the G allele of this SNP correlates with a decreased risk of the disease, while the GC genotype is linked to an increased likelihood of developing Parkinson's disease.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201493"},"PeriodicalIF":0.7,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465900","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}
Pub Date : 2025-10-13DOI: 10.1016/j.humgen.2025.201495
Joseph Faith
{"title":"Commentary on Livni & Skorecki, “Distinguishing between Founder and Host Population mtDNA Lineages in the Ashkenazi Population”","authors":"Joseph Faith","doi":"10.1016/j.humgen.2025.201495","DOIUrl":"10.1016/j.humgen.2025.201495","url":null,"abstract":"","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201495"},"PeriodicalIF":0.7,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319601","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}
Pub Date : 2025-10-13DOI: 10.1016/j.humgen.2025.201494
Ankur Datta , Esther Graceia Precious A , Akshata Shetty , Sridhar Raj S , George Priya Doss C
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.
{"title":"Utilizing explainable AI to decipher transcriptomic alterations in pancreatic cancer","authors":"Ankur Datta , Esther Graceia Precious A , Akshata Shetty , Sridhar Raj S , 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":"2025-10-13","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}
Pub Date : 2025-10-13DOI: 10.1016/j.humgen.2025.201489
Nimisha Ghosh , Walter Arancio , Tariq Al Jabry , Raya Al Maskari , Daniele Santoni
Autism Spectrum Disorders (ASD) encompass a group of neurodevelopmental disorders in which an affected individual faces challenges in social interaction and communication, along with restricted and repetitive stereotypic behavioral patterns and interests. In this work, we have studied the differential gene regulation between patients and controls, mediated by Transcription Factors (TFs), of key genes involved in ASD. Nine and seven TFs have been identified as potential regulators of the set of syndromic and non-syndromic key high confident genes retrieved by the Simons Foundation Autism Research Initiative (SFARI) database. We have also identified significant couples of Transcription Factor - Target Gene potentially associated with an altered regulation in ASD patients. Consistently, many identified couples are involved in processes associated with brain morphogenesis and development. In this regard, this biased regulation could be the target of some experimental design in order to (1) test this hypothesis and (2) try to target this altered regulation pattern in ASD samples. In conclusion, we would like to emphasize that the present work proposes an effective and reliable computational approach that could be applied to any disease with known key genes and available gene expression data.
{"title":"Transcription Factor driven gene regulation in Autism Spectrum Disorder","authors":"Nimisha Ghosh , Walter Arancio , Tariq Al Jabry , Raya Al Maskari , Daniele Santoni","doi":"10.1016/j.humgen.2025.201489","DOIUrl":"10.1016/j.humgen.2025.201489","url":null,"abstract":"<div><div>Autism Spectrum Disorders (ASD) encompass a group of neurodevelopmental disorders in which an affected individual faces challenges in social interaction and communication, along with restricted and repetitive stereotypic behavioral patterns and interests. In this work, we have studied the differential gene regulation between patients and controls, mediated by Transcription Factors (TFs), of key genes involved in ASD. Nine and seven TFs have been identified as potential regulators of the set of syndromic and non-syndromic key high confident genes retrieved by the Simons Foundation Autism Research Initiative (SFARI) database. We have also identified significant couples of Transcription Factor - Target Gene potentially associated with an altered regulation in ASD patients. Consistently, many identified couples are involved in processes associated with brain morphogenesis and development. In this regard, this biased regulation could be the target of some experimental design in order to (1) test this hypothesis and (2) try to target this altered regulation pattern in ASD samples. In conclusion, we would like to emphasize that the present work proposes an effective and reliable computational approach that could be applied to any disease with known key genes and available gene expression data.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201489"},"PeriodicalIF":0.7,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145319598","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}
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