This study explores the impact of genetic variations in two mitochondrial genes, MT-ND1 and MT-CO2 on breast cancer development. Through sequence- and structure-based bioinformatics analysis, an mt.7830 G > A (CGC > CAC) mutation in the MT-CO2 gene was identified in a 60-year-old woman as the most deleterious. This mutation leads to the substitution of a conserved arginine (R82) with histidine, potentially disrupting COX2 function. Publicly available databases highlight that arginine is the most frequently mutated amino acid in human cancers, with codons CGC, CGG, and CGT being the primary sites of substitution. The mt.7830 G > A mutation impairs oxidative phosphorylation (OXPHOS), potentially increasing reactive oxygen species (ROS) production and contributing to disease progression. Additionally, a potential genotoxic influence of arsenic on mitochondrial function cannot be excluded. The variant rs878897170 was identified in a single case. The results are best viewed as preliminary observations and confirmation in larger cohorts and experimental validation are essential to authenticate the findings of the current study.
本研究探讨了MT-ND1和MT-CO2两个线粒体基因的遗传变异对乳腺癌发展的影响。通过基于序列和结构的生物信息学分析，在一名60岁女性中鉴定出MT-CO2基因中的mt.7830 G > A （CGC >； CAC）突变是最有害的。这种突变导致保守的精氨酸（R82）被组氨酸取代，潜在地破坏了COX2的功能。公开的数据库强调精氨酸是人类癌症中最常见的突变氨基酸，密码子CGC、CGG和CGT是主要的替代位点。mt. 7830g >； A突变损害氧化磷酸化（OXPHOS），潜在地增加活性氧（ROS）的产生并促进疾病进展。此外，砷对线粒体功能的潜在遗传毒性影响也不能排除。变体rs878897170在一个案例中被识别出来。结果最好被视为初步观察结果，并在更大的队列中进行确认，实验验证对于验证当前研究的结果至关重要。
{"title":"Computational analysis of missense variants in MT-ND1 and MT-CO2 associated with breast cancer: A functional and structural impact","authors":"Rhuthuparna Malayil , Anjana Munshi , Sandeep Singh","doi":"10.1016/j.humgen.2025.201513","DOIUrl":"10.1016/j.humgen.2025.201513","url":null,"abstract":"<div><div>This study explores the impact of genetic variations in two mitochondrial genes, MT-ND1 and MT-CO2 on breast cancer development. Through sequence- and structure-based bioinformatics analysis, an mt.7830 G > A (CGC > CAC) mutation in the MT-CO2 gene was identified in a 60-year-old woman as the most deleterious. This mutation leads to the substitution of a conserved arginine (R82) with histidine, potentially disrupting COX2 function. Publicly available databases highlight that arginine is the most frequently mutated amino acid in human cancers, with codons CGC, CGG, and CGT being the primary sites of substitution. The mt.7830 G > A mutation impairs oxidative phosphorylation (OXPHOS), potentially increasing reactive oxygen species (ROS) production and contributing to disease progression. Additionally, a potential genotoxic influence of arsenic on mitochondrial function cannot be excluded. The variant rs878897170 was identified in a single case. The results are best viewed as preliminary observations and confirmation in larger cohorts and experimental validation are essential to authenticate the findings of the current study.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201513"},"PeriodicalIF":0.7,"publicationDate":"2025-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145571143","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}
Unsafe behaviors are believed to be related to genetic differences of people. The present study aimed to the relationship between unsafe behaviors and personality traits with the polymorphism of the genes involved in serotonergic system.
Methods
Safety behavior sampling technique, the short form of NEO-five factor inventory (NEO-FFI) and demographic information questionnaire were respectively used. Blood samples were collected for genotyping of the serotonin transporter gene 5-HTTLPR and MAO-B polymorphisms.
Result
Participants getting high scores in neuroticism and low scores in agreeableness and those possessing 5-HTTLPR SS and LL genotypes, as well as the XAY genotype of MAO-B A644G polymorphism, were more involved in unsafe behaviors. There was a significant association between 5-HTTLPR polymorphism in serotonin transporter of LS and SS genotype and MAO-B polymorphism in MAO-B A644G gene of XGY genotype is higher compared to the other unsafe behaviors. However, those with 5-HTTLPR LS genotype, as well as the XGY genotype of MAO-B A644G polymorphism, achieved a great score regarding agreeableness.
Conclusion
Due to the role of hereditary differences in individuals' tendency to unsafe behaviors, the results of the present study can be considered in job design wherever the ethics code allows.
{"title":"Study of the association between MAO-B and 5-HTTLPR polymorphism involved in serotonergic system with unsafe behaviors and personality traits","authors":"Zahra Alizadeh , Forough Shams , Vafa Feyzi , Ali Alboghobeish , Mostafa Pouyakian","doi":"10.1016/j.humgen.2025.201511","DOIUrl":"10.1016/j.humgen.2025.201511","url":null,"abstract":"<div><h3>Background</h3><div>Unsafe behaviors are believed to be related to genetic differences of people. The present study aimed to the relationship between unsafe behaviors and personality traits with the polymorphism of the genes involved in serotonergic system.</div></div><div><h3>Methods</h3><div>Safety behavior sampling technique, the short form of NEO-five factor inventory (NEO-FFI) and demographic information questionnaire were respectively used. Blood samples were collected for genotyping of the serotonin transporter gene <em>5-HTTLPR</em> and <em>MAO-B</em> polymorphisms.</div></div><div><h3>Result</h3><div>Participants getting high scores in neuroticism and low scores in agreeableness and those possessing 5-<em>HTTLPR</em> SS and LL genotypes, as well as the X<sub>A</sub>Y genotype of <em>MAO-B</em> A644G polymorphism, were more involved in unsafe behaviors. There was a significant association between <em>5-HTTLPR</em> polymorphism in serotonin transporter of LS and SS genotype and MAO-B polymorphism in <em>MAO-B</em> A644G gene of X<sub>G</sub>Y genotype is higher compared to the other unsafe behaviors. However, those with 5-<em>HTTLPR</em> LS genotype, as well as the X<sub>G</sub>Y genotype of <em>MAO-B</em> A644G polymorphism, achieved a great score regarding agreeableness.</div></div><div><h3>Conclusion</h3><div>Due to the role of hereditary differences in individuals' tendency to unsafe behaviors, the results of the present study can be considered in job design wherever the ethics code allows.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201511"},"PeriodicalIF":0.7,"publicationDate":"2025-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532402","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 : 2025-11-07DOI: 10.1016/j.humgen.2025.201510
Darshika Amarakoon, Seong-Ho Lee
The translocon-associated protein/signal sequence receptor (TRAP/SSR) complex, an integral membrane protein complex of the endoplasmic reticulum (ER), has emerged as a critical regulator of co-translational protein translocation, protein secretion, and cellular homeostasis. Despite its fundamental role, research on the TRAP/SSR complex in human diseases remains limited, focusing mainly on its involvement in cancer, diabetes, neurodegenerative and spinal disorders, and hepatitis B virus infection. This review summarizes recent advances in understanding TRAP/SSR function in disease pathogenesis, highlighting its pro-tumorigenic activity, regulation of insulin biosynthesis and secretion, and potential as a biomarker for early diagnosis of neurodegenerative and spine-related disorders. Furthermore, the TRAP/SSR complex facilitates the translocation and secretion of the hepatitis B e antigen, emphasizing its role in viral pathogenesis. However, substantial research gaps persist due to the novelty of this field, and the molecular mechanisms underlying TRAP/SSR-mediated disease regulation remain incompletely understood. Therefore, future investigations should aim to elucidate the mechanistic links between TRAP/SSR dysfunction and diverse pathological conditions, including metabolic, neurodegenerative, infectious, and malignant diseases. Defining disease-specific downstream effectors and interactions with ER stress pathways – particularly the unfolded protein response and ER-associated degradation – will be critical to clarifying its contribution to cellular homeostasis and disease progression. The development of targeted therapeutic strategies to modulate TRAP/SSR activity, supported by integrative multi-omics and structural biology approaches, may ultimately enable the translation of these insights into diagnostic and therapeutic applications.
{"title":"Role of the translocon-associated protein (TRAP)/signal sequence receptor (SSR) complex in the pathogenesis of human diseases","authors":"Darshika Amarakoon, Seong-Ho Lee","doi":"10.1016/j.humgen.2025.201510","DOIUrl":"10.1016/j.humgen.2025.201510","url":null,"abstract":"<div><div>The translocon-associated protein/signal sequence receptor (TRAP/SSR) complex, an integral membrane protein complex of the endoplasmic reticulum (ER), has emerged as a critical regulator of co-translational protein translocation, protein secretion, and cellular homeostasis. Despite its fundamental role, research on the TRAP/SSR complex in human diseases remains limited, focusing mainly on its involvement in cancer, diabetes, neurodegenerative and spinal disorders, and hepatitis B virus infection. This review summarizes recent advances in understanding TRAP/SSR function in disease pathogenesis, highlighting its pro-tumorigenic activity, regulation of insulin biosynthesis and secretion, and potential as a biomarker for early diagnosis of neurodegenerative and spine-related disorders. Furthermore, the TRAP/SSR complex facilitates the translocation and secretion of the hepatitis B e antigen, emphasizing its role in viral pathogenesis. However, substantial research gaps persist due to the novelty of this field, and the molecular mechanisms underlying TRAP/SSR-mediated disease regulation remain incompletely understood. Therefore, future investigations should aim to elucidate the mechanistic links between TRAP/SSR dysfunction and diverse pathological conditions, including metabolic, neurodegenerative, infectious, and malignant diseases. Defining disease-specific downstream effectors and interactions with ER stress pathways – particularly the unfolded protein response and ER-associated degradation – will be critical to clarifying its contribution to cellular homeostasis and disease progression. The development of targeted therapeutic strategies to modulate TRAP/SSR activity, supported by integrative multi-omics and structural biology approaches, may ultimately enable the translation of these insights into diagnostic and therapeutic applications.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201510"},"PeriodicalIF":0.7,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145519418","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":"Corrigendum to ‘Dysregulated of the FAM138E and CLRN1-AS1 lncRNAs could be diagnosis biomarkers in colorectal cancer’ <Human Gene 39 (2024) 201249>","authors":"Zahra Karimi , Nastaran Asghari Moghaddam , Maryam Yousefi , Mohammad Abdolvand , Atefeh Zamani , Nasrin Fatahi Dolatabadi , Maryam Peymani","doi":"10.1016/j.humgen.2025.201496","DOIUrl":"10.1016/j.humgen.2025.201496","url":null,"abstract":"","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201496"},"PeriodicalIF":0.7,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568668","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 : 2025-11-05DOI: 10.1016/j.humgen.2025.201509
{"title":"Editorial: Application and integration of Omics data in disease biology","authors":"","doi":"10.1016/j.humgen.2025.201509","DOIUrl":"10.1016/j.humgen.2025.201509","url":null,"abstract":"","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201509"},"PeriodicalIF":0.7,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145568394","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 : 2025-11-02DOI: 10.1016/j.humgen.2025.201508
Shubhrajit Barman , Senthil Kumar Ganesan
Background
Insulin-like growth factor II (IGF2) is an imprinted growth-regulatory polypeptide essential for embryonic development, tissue growth, and metabolic regulation. Variants in IGF2 have been implicated in cancer and metabolic disorders, yet the structural and functional impact of most nonsynonymous single-nucleotide polymorphisms (nsSNPs) remains uncharacterized.
Methods
We screened IGF2 coding variants from dbSNP using multiple pathogenicity predictors (SIFT, PolyPhen-2, PANTHER, SNPs&GO, Meta-SNP, PredictSNP, PMut) and structural assessment tools. Secondary structure alterations were analysed using Project HOPE, while protein–protein docking with HDOCK was performed to investigate interactions between IGF2 and IGF2R.
Results
Seven nsSNPs (C33R, R48L, R48C, G65D, C71R, R125H, and R125S) were consistently predicted to be deleterious. These substitutions were associated with a reduction in α-helical content and distortion of the overall secondary structure. Docking analysis further revealed that, with the exception of R48C, all variants exhibited decreased binding affinity compared to the wild-type IGF2 protein.
Conclusions
These seven nsSNPs represent high-priority candidates for functional validation, as computational evidence suggests potential destabilization of IGF2 structure and altered interaction with IGF2R. Our findings demonstrate the utility of in-silico pipelines for prioritizing gene variants for downstream experimental and clinical studies.
{"title":"Computational identification and structural characterization of deleterious non-synonymous SNPs in human IGF2","authors":"Shubhrajit Barman , Senthil Kumar Ganesan","doi":"10.1016/j.humgen.2025.201508","DOIUrl":"10.1016/j.humgen.2025.201508","url":null,"abstract":"<div><h3>Background</h3><div>Insulin-like growth factor II (IGF2) is an imprinted growth-regulatory polypeptide essential for embryonic development, tissue growth, and metabolic regulation. Variants in IGF2 have been implicated in cancer and metabolic disorders, yet the structural and functional impact of most nonsynonymous single-nucleotide polymorphisms (nsSNPs) remains uncharacterized.</div></div><div><h3>Methods</h3><div>We screened IGF2 coding variants from dbSNP using multiple pathogenicity predictors (SIFT, PolyPhen-2, PANTHER, SNPs&GO, Meta-SNP, PredictSNP, PMut) and structural assessment tools. Secondary structure alterations were analysed using Project HOPE, while protein–protein docking with HDOCK was performed to investigate interactions between IGF2 and IGF2R.</div></div><div><h3>Results</h3><div>Seven nsSNPs (C33R, R48L, R48C, G65D, C71R, R125H, and R125S) were consistently predicted to be deleterious. These substitutions were associated with a reduction in α-helical content and distortion of the overall secondary structure. Docking analysis further revealed that, with the exception of R48C, all variants exhibited decreased binding affinity compared to the wild-type IGF2 protein.</div></div><div><h3>Conclusions</h3><div>These seven nsSNPs represent high-priority candidates for functional validation, as computational evidence suggests potential destabilization of IGF2 structure and altered interaction with IGF2R. Our findings demonstrate the utility of in-silico pipelines for prioritizing gene variants for downstream experimental and clinical studies.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201508"},"PeriodicalIF":0.7,"publicationDate":"2025-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465870","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}
Glioblastoma (GBM) remains one of the most aggressive and therapy-refractory primary brain tumors, with patient survival exhibiting only marginal gains despite decades of intensive research and therapeutic advancement. Standard-of-care interventions, including maximal surgical resection, radiotherapy, and the alkylating agent temozolomide, confer only modest clinical benefit. The limited therapeutic efficacy is primarily attributed to pronounced intra- and intertumoral heterogeneity, the persistence of therapy-resistant glioblastoma stem-like cells, and the restrictive nature of the blood–brain barrier (BBB), which collectively impede durable treatment responses. These therapeutic challenges have intensified efforts to develop novel treatment strategies for glioblastoma. Recent advances in preclinical research increasingly leverage patient-derived stem cell and organoid models, which more faithfully recapitulate the molecular and phenotypic heterogeneity of human tumors and enable the identification of broadly effective therapeutic vulnerabilities. Emerging approaches include the exploration of histone deacetylase (HDAC) inhibitors, cyclin-dependent kinase (CDK) inhibitors, and other rationally designed small-molecule agents. In parallel, innovative drug delivery platforms such as nanoparticle-based formulations, convection-enhanced delivery, and focused ultrasound are being actively investigated to enhance blood–brain barrier permeability and improve intra-tumoral drug distribution.
Emerging therapeutic modalities, including immunotherapies such as immune checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapies, and cancer vaccines, together with oncolytic virotherapy and gene-editing technologies, are broadening the therapeutic landscape of glioblastoma. This review synthesizes current advances in preclinical and translational research, emphasizing how the convergence of personalized medicine, multi-targeted pathway inhibition, and next-generation delivery platforms may collectively enhance therapeutic efficacy and ultimately improve patient survival.
{"title":"Frontiers in glioblastoma therapy: Novel therapeutics, molecular pathways, and future clinical perspectives","authors":"Sandeep Pandey , Akanksha Dwivedi , Ranjana Singh , Nimra Habib , Dharmendra Kashyap , Vaishali Saini , Arjit Singh , Ankit Sharma , Hem Chandra Jha","doi":"10.1016/j.humgen.2025.201507","DOIUrl":"10.1016/j.humgen.2025.201507","url":null,"abstract":"<div><div>Glioblastoma (GBM) remains one of the most aggressive and therapy-refractory primary brain tumors, with patient survival exhibiting only marginal gains despite decades of intensive research and therapeutic advancement. Standard-of-care interventions, including maximal surgical resection, radiotherapy, and the alkylating agent temozolomide, confer only modest clinical benefit. The limited therapeutic efficacy is primarily attributed to pronounced intra- and intertumoral heterogeneity, the persistence of therapy-resistant glioblastoma stem-like cells, and the restrictive nature of the blood–brain barrier (BBB), which collectively impede durable treatment responses. These therapeutic challenges have intensified efforts to develop novel treatment strategies for glioblastoma. Recent advances in preclinical research increasingly leverage patient-derived stem cell and organoid models, which more faithfully recapitulate the molecular and phenotypic heterogeneity of human tumors and enable the identification of broadly effective therapeutic vulnerabilities. Emerging approaches include the exploration of histone deacetylase (HDAC) inhibitors, cyclin-dependent kinase (CDK) inhibitors, and other rationally designed small-molecule agents. In parallel, innovative drug delivery platforms such as nanoparticle-based formulations, convection-enhanced delivery, and focused ultrasound are being actively investigated to enhance blood–brain barrier permeability and improve intra-tumoral drug distribution.</div><div>Emerging therapeutic modalities, including immunotherapies such as immune checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell therapies, and cancer vaccines, together with oncolytic virotherapy and gene-editing technologies, are broadening the therapeutic landscape of glioblastoma. This review synthesizes current advances in preclinical and translational research, emphasizing how the convergence of personalized medicine, multi-targeted pathway inhibition, and next-generation delivery platforms may collectively enhance therapeutic efficacy and ultimately improve patient survival.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"47 ","pages":"Article 201507"},"PeriodicalIF":0.7,"publicationDate":"2025-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145616457","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}
Annexin A1 (AnxA1) is known to suppress inflammation by inhibiting the synthesis of pro-inflammatory molecules and promoting the release of immune-suppressive molecules. This suggests AnxA1 may be a vital marker for modulating inflammation and cell proliferation in Diabetic Foot Ulcer (DFU) patients. The current study aimed to investigate the expression and role of AnxA1 in relation to other key inflammatory molecules in DFU.
Methods
A cross-sectional study was conducted among 40 participants (20 DFU patients and 20 healthy subjects) to evaluate the expression of AnxA1, IL-10, IL-1β, IL-6, and TNF-α from both the blood and tissue samples.
Results
The mean relative expression of anti-inflammatory molecules such as AnxA1 (0.507, 0.442) and IL-10 (2.273, 0.602) were found to be downregulated in tissue and blood, respectively among DFU patients compared to healthy controls. Conversely, the pro-inflammatory molecules like IL-1β (2.393, 0.988), IL-6 (0.830, 0.748), and TNF-α (1.81, 1.099) were upregulated among DFU patients compared to healthy controls. The mean relative expression of AnxA1 and IL-1β was significantly higher in tissue and blood samples respectively of gangrenous DFU compared to non-gangrenous DFU (P < 0.05). Furthermore, AnxA1 expression showed a significant negative correlation with HbA1c and triglyceride levels (in blood and tissue) as well as wound grade and cholesterol levels (in tissue).
Conclusion
The relative down-expression of AnxA1 in DFU patients and its negative correlation with HbA1c, total cholesterol, and triglycerides indicate that AnxA1 has the potential to decrease inflammatory harm in DFU. These findings highlight AnxA1 as a promising target for novel therapeutic strategies against diabetic foot ulceration.
{"title":"Annexin A1 as a potential anti-inflammatory marker in diabetic foot ulcer: A cross-sectional study","authors":"Shwetha Shetty Kalladka , Raushan Kumar Chaudhary , Prakash Patil , Praveenkumar Shetty , Suchetha Kumari Nalilu , Abhijith Shetty","doi":"10.1016/j.humgen.2025.201505","DOIUrl":"10.1016/j.humgen.2025.201505","url":null,"abstract":"<div><h3>Background</h3><div>Annexin A1 (AnxA1) is known to suppress inflammation by inhibiting the synthesis of pro-inflammatory molecules and promoting the release of immune-suppressive molecules. This suggests AnxA1 may be a vital marker for modulating inflammation and cell proliferation in Diabetic Foot Ulcer (DFU) patients. The current study aimed to investigate the expression and role of AnxA1 in relation to other key inflammatory molecules in DFU.</div></div><div><h3>Methods</h3><div>A cross-sectional study was conducted among 40 participants (20 DFU patients and 20 healthy subjects) to evaluate the expression of AnxA1, IL-10, IL-1β, IL-6, and TNF-α from both the blood and tissue samples.</div></div><div><h3>Results</h3><div>The mean relative expression of anti-inflammatory molecules such as AnxA1 (0.507, 0.442) and IL-10 (2.273, 0.602) were found to be downregulated in tissue and blood, respectively among DFU patients compared to healthy controls. Conversely, the pro-inflammatory molecules like IL-1β (2.393, 0.988), IL-6 (0.830, 0.748), and TNF-α (1.81, 1.099) were upregulated among DFU patients compared to healthy controls. The mean relative expression of AnxA1 and IL-1β was significantly higher in tissue and blood samples respectively of gangrenous DFU compared to non-gangrenous DFU (<em>P</em> < 0.05). Furthermore, AnxA1 expression showed a significant negative correlation with HbA1c and triglyceride levels (in blood and tissue) as well as wound grade and cholesterol levels (in tissue).</div></div><div><h3>Conclusion</h3><div>The relative down-expression of AnxA1 in DFU patients and its negative correlation with HbA1c, total cholesterol, and triglycerides indicate that AnxA1 has the potential to decrease inflammatory harm in DFU. These findings highlight AnxA1 as a promising target for novel therapeutic strategies against diabetic foot ulceration.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201505"},"PeriodicalIF":0.7,"publicationDate":"2025-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465898","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 : 2025-10-30DOI: 10.1016/j.humgen.2025.201502
Md Kamal Hossain Ripon , A.K. Azad Chowdhury , Mamun Al-Mahtab , Zobaer Al Mahmud , Nahid Sharmin , Sheikh Zahir Raihan
Polymorphism of the transmembrane 6 superfamily member 2 (TM6SF2) gene influences the risk of metabolic dysfunction-associated steatotic liver disease (MASLD). It is unclear how TM6SF2 is related to the consequence of MASLD in the Bangladeshi people. This case-control study aims to determine whether the polymorphism in the TM6SF2 gene is linked with MASLD subjects in Bangladesh. Genomic DNA was isolated from peripheral blood samples. Sanger sequencing was completed for the genotype of single nucleotide polymorphisms (SNPs). SPSS was used to analyze the data for statistics. A total of 138 Bangladeshi people participated in the study. Binary logistic regression assisted in determining the link between MASLD and genetic variants. The MASLD group had a significantly higher minor allele frequency in the rs 58542926 (T), rs 72999063 (T) and rs 72999068 (G) of TM6SF2 compared to the healthy controls (P = 0.018, <0.001, 0.001, respectively). After adjusting for age and gender, the dominant model of rs 58542926 moderately elevated the risk of MASLD (OR: 3.29, 95 % CI: 1.00–10.89; P = 0.051). In our study group, rs 72999063, rs 72999068 and rs 2074299 were not found to have any significant effect on the risk of developing MASLD after adjusting for age, gender and rs 58542926. However, polymorphism rs 58542926 was found to be moderately LD (linkage disequilibrium) with both rs 72999063 and rs 72999068 (D′ = 0.804, r = 0.597, P < 0.05 and D′ = 0.746, r = 0.611, P < 0.05, respectively). Whereas rs 72999063 and rs 72999068 are strongly LD together with D′ = 0.999 and r = 0.904, P < 0.05. This study will help identify rs 58542926, rs 72999063, and rs 72999068 polymorphisms of TM6SF2 in various global populations. Further analyses are needed to better understand the effects of the TM6SF2 polymorphism on MASLD susceptibility, including a larger sample size and more physiological details.
跨膜6超家族成员2 （TM6SF2）基因多态性影响代谢功能障碍相关脂肪变性肝病（MASLD）的风险。目前尚不清楚TM6SF2与孟加拉国人患MASLD的后果有何关系。本病例对照研究旨在确定TM6SF2基因多态性是否与孟加拉国MASLD受试者有关。从外周血样本中分离基因组DNA。完成单核苷酸多态性（snp）基因型的Sanger测序。采用SPSS软件对数据进行分析统计。共有138名孟加拉国人参与了这项研究。二元逻辑回归有助于确定MASLD和遗传变异之间的联系。与健康对照组相比，MASLD组TM6SF2小等位基因rs 58542926 (T)、rs 72999063 (T)和rs 72999068 (G)的频率显著升高（P = 0.018, <0.001, 0.001）。在调整了年龄和性别后，rs 58542926的优势模型中度升高了MASLD的风险（OR: 3.29, 95% CI: 1.00-10.89; P = 0.051）。在我们的研究组中，在调整了年龄、性别和58542926后，没有发现72999063、72999068和2074299对发生MASLD的风险有任何显著影响。多态性rs 58542926与rs 72999063和rs 72999068均存在中度不平衡（D′= 0.804,r = 0.597, P < 0.05）， D′= 0.746,r = 0.611, P < 0.05)。而rs 72999063和rs 72999068是强LD，且D ' = 0.999, r = 0.904, P < 0.05。该研究将有助于确定TM6SF2在全球不同人群中的rs 58542926、rs 72999063和rs 72999068多态性。为了更好地了解TM6SF2多态性对MASLD易感性的影响，需要进一步的分析，包括更大的样本量和更多的生理细节。
{"title":"Association of transmembrane 6 superfamily member 2 rs 58542926, rs 187429064, rs 142056540, rs 72999063, rs 72999068 and rs 2074299 with susceptibility of metabolic dysfunction-associated steatotic liver disease in Bangladeshi population","authors":"Md Kamal Hossain Ripon , A.K. Azad Chowdhury , Mamun Al-Mahtab , Zobaer Al Mahmud , Nahid Sharmin , Sheikh Zahir Raihan","doi":"10.1016/j.humgen.2025.201502","DOIUrl":"10.1016/j.humgen.2025.201502","url":null,"abstract":"<div><div>Polymorphism of the transmembrane 6 superfamily member 2 (<em>TM6SF2</em>) gene influences the risk of metabolic dysfunction-associated steatotic liver disease (MASLD). It is unclear how <em>TM6SF2</em> is related to the consequence of MASLD in the Bangladeshi people. This case-control study aims to determine whether the polymorphism in the <em>TM6SF2</em> gene is linked with MASLD subjects in Bangladesh. Genomic DNA was isolated from peripheral blood samples. Sanger sequencing was completed for the genotype of single nucleotide polymorphisms (SNPs). SPSS was used to analyze the data for statistics. A total of 138 Bangladeshi people participated in the study. Binary logistic regression assisted in determining the link between MASLD and genetic variants. The MASLD group had a significantly higher minor allele frequency in the rs 58542926 (T), rs 72999063 (T) and rs 72999068 (G) of <em>TM6SF2</em> compared to the healthy controls (<em>P</em> = 0.018, <0.001, 0.001, respectively). After adjusting for age and gender, the dominant model of rs 58542926 moderately elevated the risk of MASLD (OR: 3.29, 95 % CI: 1.00–10.89; <em>P</em> = 0.051). In our study group, rs 72999063, rs 72999068 and rs 2074299 were not found to have any significant effect on the risk of developing MASLD after adjusting for age, gender and rs 58542926. However, polymorphism rs 58542926 was found to be moderately LD (linkage disequilibrium) with both rs 72999063 and rs 72999068 (D′ = 0.804, <em>r</em> = 0.597, <em>P</em> < 0.05 and D′ = 0.746, <em>r</em> = 0.611, <em>P</em> < 0.05, respectively). Whereas rs 72999063 and rs 72999068 are strongly LD together with D′ = 0.999 and <em>r</em> = 0.904, <em>P</em> < 0.05. This study will help identify rs 58542926, rs 72999063, and rs 72999068 polymorphisms of <em>TM6SF2</em> in various global populations. Further analyses are needed to better understand the effects of the <em>TM6SF2</em> polymorphism on MASLD susceptibility, including a larger sample size and more physiological details.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"46 ","pages":"Article 201502"},"PeriodicalIF":0.7,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145465872","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 : 2025-10-30DOI: 10.1016/j.humgen.2025.201506
Swapnil Kumar, Vaibhav Vindal
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.
{"title":"Estimating drivers of breast tissue transitions from normal to tumor state","authors":"Swapnil Kumar, 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":"2025-10-30","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}
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