Hypothyroidism, a prevalent endocrine disorder distinguished by inadequate thyroid hormone production, arises from a complex interplay of environmental and genetic factors. Emerging evidence implicates cytoskeletal regulation in thyroid function, with the capping actin protein of muscle Z-line subunit beta (CAPZB) gene, encoding the subunit of the F-actin capping protein, identified as a candidate gene. This study investigates the relationship between CAPZB gene polymorphism and susceptibility to hypothyroidism.
Methods
A case-control study was conducted involving 200 hypothyroid patients and 200 healthy controls. Genomic DNA was extracted and genotyped for rs12091047 using Polymerase chain reaction – Restriction fragment length polymorphism (PCR-RFLP) technique. Genotype and allele frequencies were compared between groups using Chi-square analysis.
Results
In the control group, the genotype frequency was CC (56 %), CT (43.5 %), and TT (0.5 %), while in hypothyroid patients, it was CC (41 %), CT (52 %), and TT (7 %). In the dominant model, CT and TT genotypes were significantly associated with hypothyroidism (OR- 1.831, p-value 0.0028). The recessive model showed an unstable estimate due to very low TT frequency in controls (n = 1).
Conclusion
The rs12091047 polymorphism in the CAPZB gene showed a statistical association with an increased risk of hypothyroidism in the studied population, implying that variations in cytoskeletal genes might play a role in thyroid disorders.
{"title":"CAPZB gene polymorphism and its implications for hypothyroidism: Evidence from a case-control study","authors":"Nikki Rani , Salim Khan , Anita Yadav , Ranjan Gupta","doi":"10.1016/j.genrep.2025.102422","DOIUrl":"10.1016/j.genrep.2025.102422","url":null,"abstract":"<div><h3>Background</h3><div>Hypothyroidism<strong>,</strong> a prevalent endocrine disorder distinguished by inadequate thyroid hormone production, arises from a complex interplay of environmental and genetic factors. Emerging evidence implicates cytoskeletal regulation in thyroid function, with the capping actin protein of muscle <em>Z</em>-line subunit beta (<em>CAPZB)</em> gene, encoding the subunit of the F-actin capping protein, identified as a candidate gene. This study investigates the relationship between <em>CAPZB</em> gene polymorphism and susceptibility to hypothyroidism.</div></div><div><h3>Methods</h3><div>A case-control study was conducted involving 200 hypothyroid patients and 200 healthy controls. Genomic DNA was extracted and genotyped for rs12091047 using Polymerase chain reaction – Restriction fragment length polymorphism (PCR-RFLP) technique. Genotype and allele frequencies were compared between groups using Chi-square analysis.</div></div><div><h3>Results</h3><div>In the control group, the genotype frequency was CC (56 %), CT (43.5 %), and TT (0.5 %), while in hypothyroid patients, it was CC (41 %), CT (52 %), and TT (7 %). In the dominant model, CT and TT genotypes were significantly associated with hypothyroidism (OR- 1.831, <em>p</em>-value 0.0028). The recessive model showed an unstable estimate due to very low TT frequency in controls (<em>n</em> = 1).</div></div><div><h3>Conclusion</h3><div>The rs12091047 polymorphism in the <em>CAPZB</em> gene showed a statistical association with an increased risk of hypothyroidism in the studied population, implying that variations in cytoskeletal genes might play a role in thyroid disorders.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"42 ","pages":"Article 102422"},"PeriodicalIF":0.9,"publicationDate":"2026-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145921017","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}
Periodontitis and Type 2 Diabetes Mellitus are chronic disorders with high prevalence in the population, both influenced significantly by genetic factors. Glutathione peroxidase 4, a selenoprotein, plays a key role in maintaining oxidative homeostasis.
Objectives
This study evaluated the association of the GPX4 rs713041 single-nucleotide polymorphism in the 5′ untranslated region with periodontitis, T2DM, and their co-occurrence in a South Indian cohort.
Methods
The SNP rs713041 was analysed in 300 diseased individuals and 100 healthy controls using PCR-RFLP. Additionally, the impact of the wild-type and variant rs713041 on mRNA secondary structure was studied, and molecular docking was performed to analyse the interaction of GPX4 with gingipain (Kgp).
Results
The results revealed a significant association (P < 0.05) of the heterozygous genotype T/C of rs713041 with periodontitis, T2DM, and periodontitis with T2DM. The frequency of the variant CC genotype was significantly higher in periodontitis compared to healthy controls (1.07–9.64; P < 0.05). The genotype frequencies for rs713041 adhered to the Hardy-Weinberg equilibrium in the study population (P > 0.05). Thermodynamic analysis revealed that the free energy of the rs713041 variant (−274.97 kcal/mol) was higher than that of the wild type, suggesting reduced stability of the variant. Docking analysis showed a binding energy of −47.18 kcal/mol for the -gingipain interaction.
Conclusion
The SNP rs713041 in the 5’ UTR of the GPX4 gene may serve as a significant prognostic marker for periodontitis and T2DM, highlighting its potential role in the pathogenesis of these diseases.
{"title":"Glutathione peroxidase 4 gene polymorphism and its association with periodontitis and type 2 diabetes mellitus in south Indian population","authors":"Usha Subbiah , Kaniha Sivakumar , Nihala Sidhic , Athira Ajith , Challa Raji Lalasa , Bathala Sai Dharani , Harini Venkata Subbiah , Jeyanthi Rebecca , Anitha Balaji","doi":"10.1016/j.genrep.2025.102421","DOIUrl":"10.1016/j.genrep.2025.102421","url":null,"abstract":"<div><h3>Background</h3><div>Periodontitis and Type 2 Diabetes Mellitus are chronic disorders with high prevalence in the population, both influenced significantly by genetic factors. Glutathione peroxidase 4, a selenoprotein, plays a key role in maintaining oxidative homeostasis.</div></div><div><h3>Objectives</h3><div>This study evaluated the association of the GPX<em>4</em> rs713041 single-nucleotide polymorphism in the 5′ untranslated region with periodontitis, T2DM, and their co-occurrence in a South Indian cohort.</div></div><div><h3>Methods</h3><div>The SNP rs713041 was analysed in 300 diseased individuals and 100 healthy controls using PCR-RFLP. Additionally, the impact of the wild-type and variant rs713041 on mRNA secondary structure was studied, and molecular docking was performed to analyse the interaction of <em>GPX4</em> with gingipain (Kgp).</div></div><div><h3>Results</h3><div>The results revealed a significant association (<em>P</em> < 0.05) of the heterozygous genotype T/C of rs713041 with periodontitis, T2DM, and periodontitis with T2DM. The frequency of the variant CC genotype was significantly higher in periodontitis compared to healthy controls (1.07–9.64; <em>P</em> < 0.05). The genotype frequencies for rs713041 adhered to the Hardy-Weinberg equilibrium in the study population (<em>P</em> > 0.05). Thermodynamic analysis revealed that the free energy of the rs713041 variant (−274.97 kcal/mol) was higher than that of the wild type, suggesting reduced stability of the variant. Docking analysis showed a binding energy of −47.18 kcal/mol for the <em>-</em>gingipain interaction.</div></div><div><h3>Conclusion</h3><div>The SNP rs713041 in the 5’ UTR of the <em>GPX4</em> gene may serve as a significant prognostic marker for periodontitis and T2DM, highlighting its potential role in the pathogenesis of these diseases.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"42 ","pages":"Article 102421"},"PeriodicalIF":0.9,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145880404","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}
The spermatozoon is a specialized cell that transmits not only DNA but also other molecules, which, until recently, were thought to transport the paternal genome to the oocyte solely. Recent evidences show that the sperm is responsible for delivering many other components and molecules that are essential not only in early embryonic events but might also have long-lasting effects across several generations. Non-coding RNAs (ncRNAs) carried by sperm have been implicated in fertilization, embryo and placental development, and offspring health. Meanwhile, non-coding RNAs (ncRNAs) are known to be part of dynamic epigenetic mechanisms that can rapidly change in response to various internal and external factors. Here, we provide a clinician-oriented synthesis emphasizing paternal evidence, mechanisms, and actionable gaps. We summarize insights from the current understanding of sperm epigenetic information, particularly ncRNAs, their impact on pregnancy outcomes, placental growth, development, and the possible pathways involved.
{"title":"Sperm non-coding RNAs and pregnancy outcomes: A literature review","authors":"Parisa Dolati, Emran Esmaeilzadeh, Hamid Reza Khorram Khorshid","doi":"10.1016/j.genrep.2025.102420","DOIUrl":"10.1016/j.genrep.2025.102420","url":null,"abstract":"<div><div>The spermatozoon is a specialized cell that transmits not only DNA but also other molecules, which, until recently, were thought to transport the paternal genome to the oocyte solely. Recent evidences show that the sperm is responsible for delivering many other components and molecules that are essential not only in early embryonic events but might also have long-lasting effects across several generations. Non-coding RNAs (ncRNAs) carried by sperm have been implicated in fertilization, embryo and placental development, and offspring health. Meanwhile, non-coding RNAs (ncRNAs) are known to be part of dynamic epigenetic mechanisms that can rapidly change in response to various internal and external factors. Here, we provide a clinician-oriented synthesis emphasizing paternal evidence, mechanisms, and actionable gaps. We summarize insights from the current understanding of sperm epigenetic information, particularly ncRNAs, their impact on pregnancy outcomes, placental growth, development, and the possible pathways involved.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"42 ","pages":"Article 102420"},"PeriodicalIF":0.9,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145880405","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}
Despite advances in diagnostics, preeclampsia (PE) remains a leading cause of maternal and fetal morbidity. Elucidating the molecular mechanisms underlying PE is essential for developing improved interventions. Recent evidence points to epigenetic dysregulation of HIST1H3E (H3C6) in PE placentas, characterized by decreased expression and hypermethylation. Therefore, this study investigates H3C6 expression and methylation patterns in PE placentas compared to healthy controls.
Materials and methods
We analyzed 30 PE and 30 control placental tissues. H3C6 mRNA levels were quantified by RT-qPCR, and methylation status was assessed via Methylation-Quantification of Endonuclease-Resistant DNA (MethyQESD) targeting two CpG island regions in H3C6 gene. Statistical analyses were performed using GraphPad Prism.
Results
Quantitative analysis revealed significantly reduced H3C6 mRNA expression in preeclamptic placentas compared to controls (p < 0.05). However, methylation analysis of two CpG island regions within H3C6 gene demonstrated no significant differences between groups (p > 0.05).
Conclusion
While H3C6 is underexpressed in PE, its methylation status in the analyzed CpG islands remains unaltered. Future studies should explore other regulatory regions (e.g., CpG shores/shelfs) and mechanistic links to PE pathophysiology.
{"title":"Reduced H3C6 mRNA levels in preeclamptic placentas without associated CpG island methylation changes","authors":"Majid Zaki-Dizaji , Mohsen Saravani , Behnoosh Jamshidi , Seyed Mohammad-Hossein Nemati , Marzieh Ghasemi , Zohreh Heidary","doi":"10.1016/j.genrep.2025.102419","DOIUrl":"10.1016/j.genrep.2025.102419","url":null,"abstract":"<div><h3>Background</h3><div>Despite advances in diagnostics, preeclampsia (PE) remains a leading cause of maternal and fetal morbidity. Elucidating the molecular mechanisms underlying PE is essential for developing improved interventions. Recent evidence points to epigenetic dysregulation of HIST1H3E (H3C6) in PE placentas, characterized by decreased expression and hypermethylation. Therefore, this study investigates H3C6 expression and methylation patterns in PE placentas compared to healthy controls.</div></div><div><h3>Materials and methods</h3><div>We analyzed 30 PE and 30 control placental tissues. <em>H3C6</em> mRNA levels were quantified by RT-qPCR, and methylation status was assessed via Methylation-Quantification of Endonuclease-Resistant DNA (MethyQESD) targeting two CpG island regions in H3C6 gene. Statistical analyses were performed using GraphPad Prism.</div></div><div><h3>Results</h3><div>Quantitative analysis revealed significantly reduced H3C6 mRNA expression in preeclamptic placentas compared to controls (<em>p</em> < 0.05). However, methylation analysis of two CpG island regions within H3C6 gene demonstrated no significant differences between groups (<em>p</em> > 0.05).</div></div><div><h3>Conclusion</h3><div>While H3C6 is underexpressed in PE, its methylation status in the analyzed CpG islands remains unaltered. Future studies should explore other regulatory regions (e.g., CpG shores/shelfs) and mechanistic links to PE pathophysiology.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"42 ","pages":"Article 102419"},"PeriodicalIF":0.9,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145836485","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 : 2025-12-20DOI: 10.1016/j.genrep.2025.102418
Nebiye Pelin TURKER
The aim of this study was to determine the elemental and phenolic composition of Artemisia absinthium and evaluate its hepatoprotective effects against ethanol-induced cytotoxicity in AML12 hepatocytes. Elemental analysis by ICP-MS revealed high levels of potassium, calcium, and phosphorus, along with essential trace elements such as Fe, Zn, and Cu. LC-MS/MS identified chlorogenic and protocatechuic acids as dominant phenolics. In MTT assays, ethanol significantly reduced cell viability (IC₅₀ = 15.63 %), whereas co-treatment with A. absinthium extract improved viability to 84.29 %. Gene expression analysis showed that ethanol induced ER stress and the pro-inflammatory cytokine TNF-α, which were downregulated by the extract, indicating a targeted anti-inflammatory effect. Post-treatment with A. absinthium also enhanced antioxidant gene expression (CAT, SOD, GSH). Flow cytometry confirmed reduced ROS levels in extract-treated cells. These findings suggest that A. absinthium exerts hepatoprotective effects by modulating oxidative stress, ER stress, and inflammatory signaling, highlighting the necessity for further investigation into the upstream molecular mechanisms of ROS generation.
{"title":"Phenolic and elemental composition of Artemisia absinthium and its protective role against ethanol-induced ER stress and TNF-α mediated inflammation in hepatic cells","authors":"Nebiye Pelin TURKER","doi":"10.1016/j.genrep.2025.102418","DOIUrl":"10.1016/j.genrep.2025.102418","url":null,"abstract":"<div><div>The aim of this study was to determine the elemental and phenolic composition of <em>Artemisia absinthium</em> and evaluate its hepatoprotective effects against ethanol-induced cytotoxicity in AML12 hepatocytes. Elemental analysis by ICP-MS revealed high levels of potassium, calcium, and phosphorus, along with essential trace elements such as Fe, Zn, and Cu. LC-MS/MS identified chlorogenic and protocatechuic acids as dominant phenolics. In MTT assays, ethanol significantly reduced cell viability (IC₅₀ = 15.63 %), whereas co-treatment with <em>A. absinthium</em> extract improved viability to 84.29 %. Gene expression analysis showed that ethanol induced ER stress and the pro-inflammatory cytokine TNF-α, which were downregulated by the extract, indicating a targeted anti-inflammatory effect. Post-treatment with <em>A. absinthium</em> also enhanced antioxidant gene expression (CAT, SOD, GSH). Flow cytometry confirmed reduced ROS levels in extract-treated cells. These findings suggest that <em>A. absinthium</em> exerts hepatoprotective effects by modulating oxidative stress, ER stress, and inflammatory signaling, highlighting the necessity for further investigation into the upstream molecular mechanisms of ROS generation.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"42 ","pages":"Article 102418"},"PeriodicalIF":0.9,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145836492","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 : 2025-12-19DOI: 10.1016/j.genrep.2025.102412
Leegan Govender , Nasheeta Peer , Cecil J. Weale , Don M. Matshazi , Tandi E. Matsha , Collet Dandara , Andre P. Kengne
Background
People living with human immunodeficiency virus (PLWH) have increased risk of weight gain, overweight, and obesity, and subsequent cardiometabolic diseases (CMDs). MicroRNAs (miRNAs) are emerging biomarkers for diabetes and obesity due to their regulatory roles in pathophysiological pathways leading to these conditions. In non-HIV populations, microRNAs (miR-126-3p, −223-3p, and -320a) have been associated with CMD risk.
Aim
To examine the expression patterns of targeted miRNAs (miR-126-3p, −223-3p, and -320a) with overweight/obesity status in PLWH in South Africa.
Methods
This cross-sectional study included ≥18-years-old PLWH, from 17 HIV clinics that provided antiretroviral care in the Western Cape between 2014 and 2015. Body mass index (BMI) <25 kg/m2 is defined as normal/underweight, BMI between ≥25 kg/m2 and < 30 kg/m2 is defined as overweight, and BMI ≥30 kg/m2 is defined as obesity. Whole blood miRNAs were isolated and quantified by reverse transcription polymerase chain reaction with small nucleolar RNA, C/D box 84 (SNOR D48) endogenous control used for normalisation. Statistical analyses used R software, with p-value<0.05 characterising significant results.
Results
Overall, all three target miRNAs were significantly but weakly correlated with fasting glucose (all, p < 0.046), fasting insulin (all, p < 0.015), and homeostatic model assessment-estimated insulin resistance (all, p < 0.002). Furthermore, miR-126-3p and − 223-3p were significantly correlated with 2-h insulin (both, p < 0.029) and alanine transaminase (both, p < 0.021). There were no significant differences in target miRNAs expression by BMI categories. Age and gender-adjusted regression analysis found no significant associations between the target miRNAs and CMD risk profiles.
Conclusion
The expression patterns evaluated in this study appear to have weak associations with fasting glucose and cannot differentiate overweight/obesity status in PLWH. While not promising markers for overweight/obesity in PLWH, these findings remain exploratory, and further investigation is warranted.
{"title":"Delineating miR-126-3p, miR-223-3p, and miR-320a expression patterns with body mass index and insulin resistance in South African adults living with HIV","authors":"Leegan Govender , Nasheeta Peer , Cecil J. Weale , Don M. Matshazi , Tandi E. Matsha , Collet Dandara , Andre P. Kengne","doi":"10.1016/j.genrep.2025.102412","DOIUrl":"10.1016/j.genrep.2025.102412","url":null,"abstract":"<div><h3>Background</h3><div>People living with human immunodeficiency virus (PLWH) have increased risk of weight gain, overweight, and obesity, and subsequent cardiometabolic diseases (CMDs). MicroRNAs (miRNAs) are emerging biomarkers for diabetes and obesity due to their regulatory roles in pathophysiological pathways leading to these conditions. In non-HIV populations, microRNAs (miR-126-3p, −223-3p, and -320a) have been associated with CMD risk.</div></div><div><h3>Aim</h3><div>To examine the expression patterns of targeted miRNAs (miR-126-3p, −223-3p, and -320a) with overweight/obesity status in PLWH in South Africa.</div></div><div><h3>Methods</h3><div>This cross-sectional study included ≥18-years-old PLWH, from 17 HIV clinics that provided antiretroviral care in the Western Cape between 2014 and 2015. Body mass index (BMI) <25 kg/m<sup>2</sup> is defined as normal/underweight, BMI between ≥25 kg/m<sup>2</sup> and < 30 kg/m<sup>2</sup> is defined as overweight, and BMI ≥30 kg/m<sup>2</sup> is defined as obesity. Whole blood miRNAs were isolated and quantified by reverse transcription polymerase chain reaction with small nucleolar RNA, C/D box 84 (SNOR D48) endogenous control used for normalisation. Statistical analyses used R software, with <em>p</em>-value<0.05 characterising significant results.</div></div><div><h3>Results</h3><div>Overall, all three target miRNAs were significantly but weakly correlated with fasting glucose (all, <em>p</em> < 0.046), fasting insulin (all, <em>p</em> < 0.015), and homeostatic model assessment-estimated insulin resistance (all, <em>p</em> < 0.002). Furthermore, miR-126-3p and − 223-3p were significantly correlated with 2-h insulin (both, <em>p</em> < 0.029) and alanine transaminase (both, <em>p</em> < 0.021). There were no significant differences in target miRNAs expression by BMI categories. Age and gender-adjusted regression analysis found no significant associations between the target miRNAs and CMD risk profiles.</div></div><div><h3>Conclusion</h3><div>The expression patterns evaluated in this study appear to have weak associations with fasting glucose and cannot differentiate overweight/obesity status in PLWH. While not promising markers for overweight/obesity in PLWH, these findings remain exploratory, and further investigation is warranted.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"42 ","pages":"Article 102412"},"PeriodicalIF":0.9,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145880291","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 : 2025-12-19DOI: 10.1016/j.genrep.2025.102417
Afaf M Elsaid , Yasmeen M Elsayed , Ali H. Abu Almaaty , Mohamed I. Eid , Ahmed K. Hasan
Aim
Uterine fibroids (UFs), commonly referred to as “leiomyomas,” are the most prevalent benign tumors in premenopausal females. They are often associated with infertility and recurrent miscarriage. The objective of this study was to assess the potential of cycloxygenase-2 (COX-2) gene polymorphism as a risk factor for fibroid development.
Patients and methods
This study involved 200 individuals, categorized into two groups: 100 patients with fibroids and 100 age-matched healthy females serving as the control group. Genotyping of the COX-2 (−765G>C) single nucleotide polymorphism (SNP) was conducted using the tetra-amplification refractory mutation system (T-ARMS) PCR technique.
Results
The genotype distribution patterns of the COX-2-765G>C SNP exhibited substantial variances between patients and control groups, with patients demonstrating a higher prevalence of the GC genotype (78 % versus 48 %, p < 0.001) and an increased frequency of the C-allele (47 % versus 26 %, p < 0.001). The examination of the dominant and over dominant models of the COX-2 (G>C-765) mutation demonstrated a substantial correlation with fibroid risk in comparison to controls (p < 0.001 and 0.001, respectively). The incidence of hysterectomy following fibroid diagnosis was markedly elevated in the dominant model group 3 (p = 0.02), whereas 3the incidence of myomectomy was much greater in the recessive model group (p < 0.001).
Conclusions
A substantial correlation was identified between the −765G>C SNP in the COX-2 gene and uterine leiomyoma in Egyptian females, indicating that its potential regulatory role merits further examination. Identifying the genes associated with UFs may result in novel medications and maybe the avoidance of this condition.
{"title":"Cycloxygenase-2 (−765G>C) gene polymorphism and risk of uterine fibroids in Egyptian women","authors":"Afaf M Elsaid , Yasmeen M Elsayed , Ali H. Abu Almaaty , Mohamed I. Eid , Ahmed K. Hasan","doi":"10.1016/j.genrep.2025.102417","DOIUrl":"10.1016/j.genrep.2025.102417","url":null,"abstract":"<div><h3>Aim</h3><div>Uterine fibroids (UFs), commonly referred to as “leiomyomas,” are the most prevalent benign tumors in premenopausal females. They are often associated with infertility and recurrent miscarriage. The objective of this study was to assess the potential of cycloxygenase-2 (COX-2) gene polymorphism as a risk factor for fibroid development.</div></div><div><h3>Patients and methods</h3><div>This study involved 200 individuals, categorized into two groups: 100 patients with fibroids and 100 age-matched healthy females serving as the control group. Genotyping of the COX-2 (−765G>C) single nucleotide polymorphism (SNP) was conducted using the tetra-amplification refractory mutation system (T-ARMS) PCR technique.</div></div><div><h3>Results</h3><div>The genotype distribution patterns of the <em>COX-2</em>-765G>C SNP exhibited substantial variances between patients and control groups, with patients demonstrating a higher prevalence of the GC genotype (78 % versus 48 %, <em>p</em> < 0.001) and an increased frequency of the C-allele (47 % versus 26 %, p < 0.001). The examination of the dominant and over dominant models of the COX-2 (G>C-765) mutation demonstrated a substantial correlation with fibroid risk in comparison to controls (<em>p</em> < 0.001 and 0.001, respectively). The incidence of hysterectomy following fibroid diagnosis was markedly elevated in the dominant model group 3 (<em>p</em> = 0.02), whereas 3the incidence of myomectomy was much greater in the recessive model group (<em>p</em> < 0.001).</div></div><div><h3>Conclusions</h3><div>A substantial correlation was identified between the −765G>C SNP in the COX-2 gene and uterine leiomyoma in Egyptian females, indicating that its potential regulatory role merits further examination. Identifying the genes associated with UFs may result in novel medications and maybe the avoidance of this condition.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"42 ","pages":"Article 102417"},"PeriodicalIF":0.9,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145921115","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 : 2025-12-18DOI: 10.1016/j.genrep.2025.102414
Suleiman Kolawole Yusuf , Abdulmajeed Isiaku , Adamu Abdul Abubakar , Nwachukwu Raymond Chinedu , Abdulfatai Aremu , Okediran Babatunde Samuel , Alhaji Zubair Jaji
Osteoporosis remains a major global health challenge characterized by bone fragility and limited regenerative capacity. Extracellular vesicles (EVs) have recently emerged as potent mediators of intercellular communication, capable of modulating bone remodeling through their protein cargo. Unlike prior reviews that emphasize RNA or general regenerative mechanisms, this article provides a protein-centric synthesis of how EV-associated proteins orchestrate osteoblast and osteoclast regulation via canonical pathways, including TGF-beta/Smad, MAPK, Wnt/beta-catenin, and PI3K/Akt. By integrating evidence from 60 in vitro, in vivo, and early clinical studies, we identify consistent trends that demonstrate mesenchymal stem cell-derived EVs promote osteoblast differentiation and mineralization while suppressing osteoclastogenesis, with delivery via hydrogels and scaffolds enhancing local retention and efficacy. Beyond summarizing preclinical data, this review highlights mechanistic convergence among EV protein cargo, comparative efficacy of delivery strategies, and a roadmap for translation addressing standardization, scalability, and regulatory challenges. Collectively, these insights position EV-associated proteins as versatile therapeutic effectors capable of bridging the gap between cellular therapy and precision drug delivery for osteoporosis.
{"title":"Harnessing extracellular vesicle-associated proteins for osteoporosis: Mechanisms, therapeutic strategies, and clinical potential","authors":"Suleiman Kolawole Yusuf , Abdulmajeed Isiaku , Adamu Abdul Abubakar , Nwachukwu Raymond Chinedu , Abdulfatai Aremu , Okediran Babatunde Samuel , Alhaji Zubair Jaji","doi":"10.1016/j.genrep.2025.102414","DOIUrl":"10.1016/j.genrep.2025.102414","url":null,"abstract":"<div><div>Osteoporosis remains a major global health challenge characterized by bone fragility and limited regenerative capacity. Extracellular vesicles (EVs) have recently emerged as potent mediators of intercellular communication, capable of modulating bone remodeling through their protein cargo. Unlike prior reviews that emphasize RNA or general regenerative mechanisms, this article provides a protein-centric synthesis of how EV-associated proteins orchestrate osteoblast and osteoclast regulation via canonical pathways, including TGF-beta/Smad, MAPK, Wnt/beta-catenin, and PI3K/Akt. By integrating evidence from 60 in vitro, in vivo, and early clinical studies, we identify consistent trends that demonstrate mesenchymal stem cell-derived EVs promote osteoblast differentiation and mineralization while suppressing osteoclastogenesis, with delivery via hydrogels and scaffolds enhancing local retention and efficacy. Beyond summarizing preclinical data, this review highlights mechanistic convergence among EV protein cargo, comparative efficacy of delivery strategies, and a roadmap for translation addressing standardization, scalability, and regulatory challenges. Collectively, these insights position EV-associated proteins as versatile therapeutic effectors capable of bridging the gap between cellular therapy and precision drug delivery for osteoporosis.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"42 ","pages":"Article 102414"},"PeriodicalIF":0.9,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145836491","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 : 2025-12-17DOI: 10.1016/j.genrep.2025.102415
Athanasios Lattos , Stéphane Coupé , Dimitrios K. Papadopoulos , Ioannis A. Giantsis
Scientific community is currently witnessing one of the most dynamic extinction risks, i.e. that of the largest bivalve mollusk of the Mediterranean, Pinna nobilis. The role of possible different pathogens responsible for the mass mortalities driving this extinction risk represent a considerable debate among researchers. After extensive investigation of the etiological agents, by means of numerous microbiological, pathophysiological, environmental studies, as well as efforts to identify surviving populations, current research is attempting to focus on the characterization of resistant genotypes that could enable future recruitment. Recently, the first characterization of the genomic architecture of Toll-like receptor (TLRs) genes in the genus Pinna identified potential SNPs associated with disease resistance and, hence, with genotypes tolerant to mortalities. Nevertheless, gene characterization is a challenging task that requires investigation at multiple levels, including gene expression under different stressors. In this context, the present study investigates TLR gene transcription in Pinna nobilis populations infected by different pathogens, comparing single infection with co-infection. In a general agreement with the proposed role of TLR4 and TLR6 which host SNPs associated with resistant or susceptible Pinna genotypes, the current results demonstrate a statistically significant increased transcription of these genes in individuals infected with both Mycobacterium sp. and Haplosporidium pinnae, the two mostly accused pathogens, compared with specimens infected with Mycobacterium sp. solely. Since analyses were only based on mantle tissue, these transcriptional associations require confirmation by multi-tissue and protein-level studies to clarify the functional role of TLRs in Pinna nobilis immunity and disease resistance. To this end, after examination of a large number, 11 primer pairs were validated in terms of efficiency and stability and are proposed for usage in other populations as well.
{"title":"Transcriptional regulation of Toll-like Receptors in Pinna nobilis: Insights into immune response under varying pathogen loads and effect of individual variation","authors":"Athanasios Lattos , Stéphane Coupé , Dimitrios K. Papadopoulos , Ioannis A. Giantsis","doi":"10.1016/j.genrep.2025.102415","DOIUrl":"10.1016/j.genrep.2025.102415","url":null,"abstract":"<div><div>Scientific community is currently witnessing one of the most dynamic extinction risks, i.e. that of the largest bivalve mollusk of the Mediterranean, <em>Pinna nobilis</em>. The role of possible different pathogens responsible for the mass mortalities driving this extinction risk represent a considerable debate among researchers. After extensive investigation of the etiological agents, by means of numerous microbiological, pathophysiological, environmental studies, as well as efforts to identify surviving populations, current research is attempting to focus on the characterization of resistant genotypes that could enable future recruitment. Recently, the first characterization of the genomic architecture of Toll-like receptor (TLRs) genes in the genus <em>Pinna</em> identified potential SNPs associated with disease resistance and, hence, with genotypes tolerant to mortalities. Nevertheless, gene characterization is a challenging task that requires investigation at multiple levels, including gene expression under different stressors. In this context, the present study investigates TLR gene transcription in <em>Pinna nobilis</em> populations infected by different pathogens, comparing single infection with co-infection. In a general agreement with the proposed role of TLR4 and TLR6 which host SNPs associated with resistant or susceptible <em>Pinna</em> genotypes, the current results demonstrate a statistically significant increased transcription of these genes in individuals infected with both <em>Mycobacterium</em> sp. and <em>Haplosporidium pinnae</em>, the two mostly accused pathogens, compared with specimens infected with <em>Mycobacterium</em> sp. solely. Since analyses were only based on mantle tissue, these transcriptional associations require confirmation by multi-tissue and protein-level studies to clarify the functional role of TLRs in <em>Pinna nobilis</em> immunity and disease resistance. To this end, after examination of a large number, 11 primer pairs were validated in terms of efficiency and stability and are proposed for usage in other populations as well.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"42 ","pages":"Article 102415"},"PeriodicalIF":0.9,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145836429","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 : 2025-12-17DOI: 10.1016/j.genrep.2025.102416
Fatima Malik, Mahnoor Malik, Tehsin Fatma, Muhammad Faraz Bhatti
Background
Fusarium oxysporum is an important phytopathogenic fungus causing severe vascular wilts, rots, and damping off diseases in economically important plants. Mitogenomes have a very essential role in evolutionary biology, diversity and pathogenicity of organisms. This study is focused on the characterization of the complete mitochondrial genome of F. oxysporum strain P2A and its comparative analysis with the previously published Fusarium mitogenomes. High-throughput Illumina sequencing technology enabled the complete assembly and annotation of mitochondrial genome.
Results
The reported F. oxysporum strain P2A mitogenome is composed of a circular DNA molecule with a genome size of 46,257 bp and GC content of 32.7 %. It encodes 16 protein-coding genes (PCGs), 2 ribosomal RNA (rRNA) genes, 24 transfer RNA genes and 32 open reading frames encoding hypothetical proteins. Furthermore, group IB intron encoding a homing endonuclease (LAGLIDADG) was also found in the coding region of the mitogenome, indicating its dynamic structure. Comparative mitochondrial genomic analysis with six other closely related Fusarium species revealed that GC content, gene length, GC skew, and AT skew varied among core PCGs. The gene synteny analysis of Fusarium species showed several gene rearrangements. Among the 16 PCGs, nad4, nad4L, nad6 and cob had the lowest K2P genetic distance, indicating that these genes are highly conserved. Furthermore, it was observed that the majority of PCGs possessed Ka/Ks values below 1, suggesting that these genes were subjected to purifying selection. Phylogenetic analysis based on cox2 gene revealed that F. oxysporum strain P2A is most closely related to Fusarium verticillioids in the clade containing Leotiomycetes species.
Conclusions
The complete mitogenome of F. oxysporum strain P2A and its comparative analysis will contribute to the fast-evolutionary analysis and population genetics studies among Fusarium species.
{"title":"Characterization of the mitochondrial genome of Fusarium oxysporum and comparative insights into Fusarium spp. mitochondrial evolution","authors":"Fatima Malik, Mahnoor Malik, Tehsin Fatma, Muhammad Faraz Bhatti","doi":"10.1016/j.genrep.2025.102416","DOIUrl":"10.1016/j.genrep.2025.102416","url":null,"abstract":"<div><h3>Background</h3><div><em>Fusarium oxysporum</em> is an important phytopathogenic fungus causing severe vascular wilts, rots, and damping off diseases in economically important plants. Mitogenomes have a very essential role in evolutionary biology, diversity and pathogenicity of organisms. This study is focused on the characterization of the complete mitochondrial genome of <em>F. oxysporum strain P2A</em> and its comparative analysis with the previously published <em>Fusarium</em> mitogenomes. High-throughput Illumina sequencing technology enabled the complete assembly and annotation of mitochondrial genome.</div></div><div><h3>Results</h3><div>The reported <em>F. oxysporum strain P2A</em> mitogenome is composed of a circular DNA molecule with a genome size of 46,257 bp and GC content of 32.7 %. It encodes 16 protein-coding genes (PCGs), 2 ribosomal RNA (rRNA) genes, 24 transfer RNA genes and 32 open reading frames encoding hypothetical proteins. Furthermore, group IB intron encoding a homing endonuclease (LAGLIDADG) was also found in the coding region of the mitogenome, indicating its dynamic structure. Comparative mitochondrial genomic analysis with six other closely related <em>Fusarium</em> species revealed that GC content, gene length, GC skew, and AT skew varied among core PCGs. The gene synteny analysis of <em>Fusarium</em> species showed several gene rearrangements. Among the 16 PCGs, <em>nad4, nad4L, nad6</em> and <em>cob</em> had the lowest K2P genetic distance, indicating that these genes are highly conserved. Furthermore, it was observed that the majority of PCGs possessed Ka/Ks values below 1, suggesting that these genes were subjected to purifying selection. Phylogenetic analysis based on <em>cox2</em> gene revealed that <em>F. oxysporum strain P2A</em> is most closely related to <em>Fusarium verticillioids</em> in the clade containing <em>Leotiomycetes</em> species.</div></div><div><h3>Conclusions</h3><div>The complete mitogenome of <em>F. oxysporum strain P2A</em> and its comparative analysis will contribute to the fast-evolutionary analysis and population genetics studies among <em>Fusarium</em> species.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"42 ","pages":"Article 102416"},"PeriodicalIF":0.9,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145836493","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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