Gene Reports最新文献

{"title":"MTHFR C677T and HLA-DR3/4 genetic variants: Insights into their contribution to type 1 diabetes","authors":"Shobana Manoharan ,&nbsp;Gunavathy Nagarajan ,&nbsp;Aarthy Amuthavel ,&nbsp;Thirunavukkarasu Ramasamy ,&nbsp;Chitra Ayyappan ,&nbsp;Arthur Asirvatham ,&nbsp;Jayalakshmi Mariakuttikan","doi":"10.1016/j.genrep.2025.102375","DOIUrl":"10.1016/j.genrep.2025.102375","url":null,"abstract":"<div><div>Type 1 diabetes (T1D) is an autoimmune condition with a global prevalence of approximately 9 million cases. The HLA-DR3 and DR4 alleles have a closer association with T1D and the MTHFR gene polymorphism is an emerging potential risk factor in T1D. Hence, this study aimed to explore the potential genetic impact of the MTHFR C677T polymorphism, in combination with HLADR3and DR4 alleles, towards the development of T1D. In this pilot study, a total of 193 individuals (94 patients and 99 healthy individuals) were analyzed for MTHFR C677T polymorphism and HLA-DR3/4 alleles using RT-PCR and PCR-SSP, respectively. Allele and genotype frequencies were compared between the patient and healthy individuals. Increased frequencies of HLA-DR3 and DR4 alleles were observed in patients (OR = 3.4, pc = 0.0032), and the dominant model (OR = 0.36, pc = 0.00075) of the MTHFR gene was found to be associated with T1D. Combined analysis of MTHFR genotypes and HLA-DR3/4 alleles revealed higher frequencies of specific genotype-allele combinations among patients. Furthermore, meta-analysis suggested that the dominant genetic model of MTHFR C677T polymorphism could increase the risk of T1D. Our results indicate that MTHFR C677T polymorphism and HLA-DR3/4 alleles play important roles in genetic susceptibility towards T1D and provide preliminary evidence to support future large-scale studies.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102375"},"PeriodicalIF":0.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145525826","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":"Suppression of the long non-coding RNA, Malat1, enhances epithelial morphogenesis and differentiation in the fetal mouse submandibular gland","authors":"Toru Hayashi ,&nbsp;Nonoka Nishimori ,&nbsp;Kei Eto ,&nbsp;Megumi Inomata ,&nbsp;Masahiro Fukaya","doi":"10.1016/j.genrep.2025.102377","DOIUrl":"10.1016/j.genrep.2025.102377","url":null,"abstract":"<div><div>During development, organogenesis, including gene expression control, regulated hierarchically. The genome contains regions that do not encode functional, continuous amino acid sequences, transcribing short and long non-coding RNAs. These non-coding RNAs are increasingly recognized for their involvement in diverse biological processes. <em>Malat1</em>, a long non-coding RNA (lncRNA), is extensively studied; however, its role in organogenesis is unclear. This study investigated <em>Malat1</em> expression and its contribution to organogenesis using the fetal mouse submandibular gland as a model of epithelial organ development. Developmental changes in <em>Malat1</em> expression and localization were assessed using gene expression quantification and <em>in situ</em> hybridization. Stage-dependent variation across tissue, cellular, and subcellular levels, predominantly cytoplasmic localization in epithelial cells at embryonic day 13, were observed. Suppressing <em>Malat1</em> expression in cultured isolated epithelium increased the number and width of terminal buds, indicating enhanced morphogenesis. Gene expression analysis during <em>Malat1</em> inhibition upregulated fibroblast growth factor signaling-related genes, differentiation marker genes, and downregulated progenitor marker expression. These findings suggest that <em>Malat1</em> plays a regulatory and physiological role in SMG development, influencing epithelial differentiation and morphogenesis.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102377"},"PeriodicalIF":0.9,"publicationDate":"2025-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145462423","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":"Temporal expression patterns of SnRK1 and WRKY3 defense genes reveal cultivar-specific responses to tomato curly stunt virus infection","authors":"Antzel Theron ,&nbsp;Farhahna Allie","doi":"10.1016/j.genrep.2025.102373","DOIUrl":"10.1016/j.genrep.2025.102373","url":null,"abstract":"<div><div>Tomato curly stunt virus (ToCSV) significantly impacts tomato production globally, yet the molecular mechanisms underlying cultivar-specific resistance responses remain poorly understood. We investigated the temporal expression of two key defense-related genes, Sucrose Non-Fermenting 1-Related Protein Kinase 1 (<em>SnRK1</em>) and WRKY transcription factor 3 (<em>WRKY3</em>), across four tomato cultivars with varying susceptibility to ToCSV: susceptible (Rooikhaki, Moneymaker), tolerant (NIL396), and resistant (ESTY). Using quantitative real-time PCR, we analyzed gene expression at 8, 15, and 35 days post-infection, representing early infection, symptom onset, and systemic viral movement stages. Viral quantification revealed distinct accumulation patterns, with susceptible cultivars showing 283–440 % increases in viral load between 15 and 35 dpi, while the tolerant cultivar maintained stable levels and the resistant cultivar remained undetectable. <em>SnRK1</em> expression patterns differed between cultivars: susceptible lines showed initial downregulation (15 dpi) followed by upregulation (35 dpi), while the resistant cultivar exhibited consistent downregulation. <em>WRKY3</em> displayed complex temporal patterns, with most cultivars showing early upregulation followed by late-stage downregulation, except the resistant cultivar, which maintained downregulation throughout. These results provide the first comparative temporal analysis of defense gene expression in the tomato-ToCSV pathosystem and suggest that resistance mechanisms involve distinct regulatory strategies rather than simple gene activation patterns.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102373"},"PeriodicalIF":0.9,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145462417","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":"Molecular insights of a novel Angiotensinogen homolog of Sebastes Schlegelii, revealing its transcriptional sensitivity to pathogenic infections","authors":"Don Anushka Sandaruwan Elvitigala ,&nbsp;Jehee Lee","doi":"10.1016/j.genrep.2025.102371","DOIUrl":"10.1016/j.genrep.2025.102371","url":null,"abstract":"<div><div>Angiotensinogen (AGT) is a key component in renin-angiotensin system (RAS) in animals and primarily secreted as a precursor molecule. AGTs are known to play multiple roles in animals including maintaining homeostasis and mediating host immune responses as an acute phase protein. In this study complete coding sequence of AGT homolog with 1380 bps was identified from S<em>. schlegelii</em> and designated as SsAGT. The gene codes for a protein with 460 amino acids with a predicted molecular weight of 51.3 kDa. SsAGT resembled the common domain architecture of serpin family proteins and found to bear a signal peptide of 19 residues. Protein level sequence comparison revealed the homology of SsAGT with its known counterparts of teleosts and tetrapods and phylogenetic analysis confirmed its close evolutionary relationship with teleostan orthologues. Transcriptional profile of <em>SsAGT</em> in different tissues of the healthy fish obtained by using qPCR showed a constitutive expression in selected tissues with more pronounced expression level in liver tissues. However, its basal mRNA expression in liver tissues was found to be modulated by lipopolysaccharides, Poly I:C and live <em>Streptococus iniae</em> treatments, at different time points post treatment, suggesting its potential role under pathogenic stress. These findings highlight the immunophysiological significance of AGTs in teleosts and warrant further functional studies to elucidate their role in first-line host defense mechanisms.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102371"},"PeriodicalIF":0.9,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412786","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":"Modulation of inflammatory gene expression by probiotics: A systematic review and meta-analysis of randomized controlled trials","authors":"Yaser Mohammadi ,&nbsp;Shirin Teymouri-Nobari ,&nbsp;Katayoon Asgari ,&nbsp;Soudabeh Fallah ,&nbsp;Omid Joodi-khanghah","doi":"10.1016/j.genrep.2025.102370","DOIUrl":"10.1016/j.genrep.2025.102370","url":null,"abstract":"<div><h3>Background</h3><div>Inflammation is a vital immune response that, while protecting the body, plays a significant role in the progression of non-communicable diseases when it becomes chronic. Given the conflicting evidence on the effect of probiotics on inflammatory gene expression, this meta-analysis aims to provide a comprehensive evaluation of their impact on the regulation of inflammatory genes in RCTs.</div></div><div><h3>Methods</h3><div>SCOPUS, EMBASE, PubMed, and Web of Science databases were systematically searched using standard keywords up to Feb 2025. Article selection and data extraction were conducted independently by two researchers. The quality assessment of the studies was performed using the ROB.</div></div><div><h3>Results</h3><div>A total of 9 RCTs with 197 interventions and 183 control participants were included in this meta-analysis. Probiotic supplementation significantly reduced the expression of TNF-α (SMD = −0.83; 95 % CI: −1.34, −0.31), IL-1 (SMD = −1.16; 95 % CI: −2.02, −0.30), and IL-8 (SMD = −1.40; 95 % CI: −2.64, −0.16), while no significant changes were observed in IL-10 expression (SMD = −0.06; 95 % CI: −1.05, 0.92).</div></div><div><h3>Conclusion</h3><div>This meta-analysis demonstrated that probiotic supplementation can potentially reduce the expression of inflammatory genes, including TNF-α, IL-1, and IL-8. Therefore, probiotics may be considered a potential adjunct therapy for reducing inflammation. However, further human studies are needed to better understand the therapeutic potential of probiotic supplements.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102370"},"PeriodicalIF":0.9,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145462424","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":"Comparative analysis of Staphylococcus aureus, and non-aureus staphylococci and mammaliicocci (NASM) in bovine milk: Species distribution, resistance profiling and genomic characterisation","authors":"Mehul D. Shrimali ,&nbsp;Harshad C. Chauhan ,&nbsp;Sandip S. Patel ,&nbsp;Janki D. Panchal ,&nbsp;Arun C. Patel ,&nbsp;Kishan K. Sharma ,&nbsp;Aakash K. Thakore ,&nbsp;Sushil K. Mohapatra ,&nbsp;Bhavesh I. Prajapati","doi":"10.1016/j.genrep.2025.102372","DOIUrl":"10.1016/j.genrep.2025.102372","url":null,"abstract":"<div><h3>Purpose</h3><div>This study investigates the prevalence, antibiotic resistance, and methicillin resistance (MR) patterns of <em>Staphylococcus aureus</em>, and non-aureus staphylococci and mammaliicocci (NASM) in bovine milk.</div></div><div><h3>Methods</h3><div>A total of 402 milk samples from cows and buffaloes, both healthy and mastitic, were analysed. Staphylococcal isolates were identified using conventional methods, PCR, and MALDI-TOF. Antibiotic susceptibility testing and methicillin resistance detection were performed using agar-based methods and PCR targeting <em>mec</em>A/<em>mec</em>C genes. Whole-genome sequencing (WGS) was carried out on two <em>Staphylococcus epidermidis</em> isolates.</div></div><div><h3>Results</h3><div>Among 402 samples, 134 (33.3%) yielded <em>Staphylococcus</em> spp., with <em>S. aureus</em> (52.23 %) being the most common coagulase-positive species. Predominant NASM species included <em>S. chromogenes</em> (11.19%), <em>S. epidermidis</em> (7.46 %), and <em>S. sciuri</em> (5.22 %), with <em>S. sciuri</em> now reclassified under <em>Mammaliicoccus</em>. Among the tested isolates, 57.46 % were resistant to penicillin G and 35.82 % to cefoxitin, whereas the highest proportion of susceptible isolates was observed with tetracycline (73.88 %) and chloramphenicol (73.13 %). Thirty isolates exhibited multidrug resistance, including three pan-resistant strains. Methicillin-resistant Staphylococci (MRS) were detected in 17.91 % and 23.13 % of isolates via oxacillin agar and CHROMagar, respectively. The <em>mec</em>A gene was present in 14.92 % of isolates, with varying prevalence across Methicillin-Resistant Coagulase-Positive <em>Staphylococcus aureus</em> (MRCoPSA) (47.36 %), Methicillin-Resistant Coagulase-Negative <em>Staphylococcus aureus</em> (MRCoNSA) (37.5 %), and Methicillin-Resistant Coagulase-Negative Staphylococci (MRCoNS) (66.66 %); no isolate harboured <em>mec</em>C. <em>S</em><em>taphylococcus epidermidis</em> strains SKN228 and SKN421 revealed ∼2.4 Mb genomes, a G + C content of ∼32 %, and resistance genes (<em>bla</em>Z, <em>van</em>T, <em>mec</em>A, <em>mec</em>D) associated with efflux pumps, enzymatic inactivation, and target modification in WGS.</div></div><div><h3>Conclusions</h3><div>These findings underscore the emerging significance of NASM in bovine mastitis and highlight the need for further study on <em>mec</em>-independent methicillin resistance mechanisms.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102372"},"PeriodicalIF":0.9,"publicationDate":"2025-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145462427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of the RNASE9 c.1+1G>A splice site variant with decreased sperm motility in Japanese men","authors":"Shinichiro Saeki ,&nbsp;Junko Otsuki ,&nbsp;Noritoshi Enatsu ,&nbsp;Xingqiang Wei ,&nbsp;Naoto Mukaida ,&nbsp;Ryota Okamoto ,&nbsp;Saori Yoshimura ,&nbsp;Keisuke Okada ,&nbsp;Koji Chiba ,&nbsp;Shoji Kokeguchi ,&nbsp;Toshiroh Iwasaki ,&nbsp;Yasuhiro Fujiwara ,&nbsp;Mikiya Nakatsuka ,&nbsp;Tetsuo Kunieda ,&nbsp;Masahide Shiotani","doi":"10.1016/j.genrep.2025.102366","DOIUrl":"10.1016/j.genrep.2025.102366","url":null,"abstract":"<div><div>This study aims to investigate the role of the <em>RNASE9</em> gene mutation (c.1 + 1G &gt; A) in male infertility, specifically focusing on its impact on sperm motility in patients with asthenozoospermia. Despite known genetic causes for azoospermia, the genetic basis of asthenozoospermia remains poorly understood. Given that <em>RNASE9</em> is specifically expressed in the epididymis, where sperm maturation occurs, we hypothesized that mutations in <em>RNASE9</em> might influence post-testicular sperm maturation. Whole-exome sequencing (WES) was performed on 20 Japanese patients with abnormal semen parameters to identify high-impact genetic variants. Variants were filtered based on allele frequencies in the 1000 Genomes Phase 3 East Asian (EAS) population and the Japanese 38KJPN database. <em>RNASE9</em> was selected for further analysis, and the presence of the c.1 + 1G &gt; A variant was confirmed in a cohort of 71 patients via Sanger sequencing. Sperm motility and other semen parameters were evaluated, and allele frequencies in asthenozoospermic, azoospermic, and normospermic groups were compared. The allele frequency of the <em>RNASE9</em> (c.1 + 1G &gt; A) variant was significantly higher in asthenozoospermic patients than in individuals with normal semen parameters (<em>p</em> = 0.022), while no significant difference was found in azoospermic patients. This suggests that the <em>RNASE9</em> variant primarily affects sperm motility rather than sperm production. The <em>RNASE9</em> (c.1 + 1G &gt; A) mutation may contribute to reduced sperm motility in humans, likely impacting post-testicular sperm maturation. The findings provide new insights into the genetic factors affecting sperm motility, particularly in asthenozoospermia.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102366"},"PeriodicalIF":0.9,"publicationDate":"2025-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145462425","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":"Detection of Epstein-Barr virus coinfections based on LMP-1 gene diversity obtained by the high-throughput sequencing","authors":"Marija Rozman ,&nbsp;Ana Planinić ,&nbsp;Kristian Bodulić ,&nbsp;Dijana Škorić ,&nbsp;Paola Gršković ,&nbsp;Anita Stojanović Marković ,&nbsp;Petra Korać ,&nbsp;Snježana Židovec-Lepej","doi":"10.1016/j.genrep.2025.102369","DOIUrl":"10.1016/j.genrep.2025.102369","url":null,"abstract":"<div><h3>Background</h3><div>Epstein-Barr virus (EBV) exhibits significant molecular diversity, commonly classified into distinct variants based on specific polymorphisms in the latent membrane protein-1 (LMP-1) gene. Traditional analyses have largely relied on Sanger sequencing, which may be limited in detecting mixed variant populations and recombination events.</div></div><div><h3>Objectives</h3><div>This study aimed to evaluate whether high-throughput sequencing (HTS) using Oxford Nanopore Technology (ONT) provides a more comprehensive analysis of LMP-1 variants, particularly in samples previously identified as recombinants by Sanger sequencing.</div></div><div><h3>Study design</h3><div>Twenty-four peripheral blood samples from patients with EBV-associated infectious mononucleosis (IM), previously analysed by Sanger sequencing, were reevaluated using full-length LMP-1 sequencing via ONT.</div></div><div><h3>Results</h3><div>ONT sequencing enabled the reclassification of 11 samples initially identified as recombinants by Sanger sequencing as coinfections, based on the presence of dual polymorphisms at the same nucleotide positions. The remaining 12 samples showed concordant results with Sanger data, confirming their recombinant nature. Additionally, ONT identified an amino acid substitution at position 366 in 5/24 samples, leading to further reclassification of LMP-1 variants. In one case, ONT detected only a single LMP-1 variant (China1), contradicting earlier recombinant classification.</div></div><div><h3>Conclusions</h3><div>ONT-based HTS enables more detailed detection of LMP-1 recombinants and coinfections, offering a broader view of EBV molecular diversity compared to Sanger sequencing. This approach has potential implications for identifying high-risk EBV variants associated with malignancy and demonstrates feasibility for implementation in routine clinical virology. To our knowledge, this is the first study to apply ONT for comprehensive molecular analysis of EBV LMP-1 coinfections.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102369"},"PeriodicalIF":0.9,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412790","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":"Genetic polymorphisms associated with Behçet's disease in Egypt, Tunisia, and Morocco: A systematic review","authors":"Kahli Zineb ,&nbsp;Ait Baha Atmane ,&nbsp;Habbane Mouna ,&nbsp;Hassani Idrissi Hind ,&nbsp;El Bassyouni Najlâa ,&nbsp;Moudatir Mina ,&nbsp;Semlali Mohammed Youssef ,&nbsp;Akhouayri Omar","doi":"10.1016/j.genrep.2025.102368","DOIUrl":"10.1016/j.genrep.2025.102368","url":null,"abstract":"<div><div>This systematic review examines the genetic polymorphisms associated with Behcet disease in Africa, focusing on SNPs and HLA class I and II gene variants. A structured search was conducted in the PubMed, Scopus, Web of Science, and ScienceDirect databases, according to rigorous inclusion and exclusion criteria. The analysis shows that Egypt is the most active country in terms of publications, followed by Tunisia and Morocco. Certain genes were analyzed collectively in all three countries. The CTLA-4 + 49 A variant was more at risk in Tunisia (OR = 4.63) and Egypt (OR = 3.08), showing a high association with disease susceptibility. Other variants, such as VDR-<em>Apa</em>I-a (OR = 2.09 in Egypt) and VDR-<em>Fok</em>I-F (OR = 1.89 in Tunisia), have moderate associations. Inflammation-related polymorphisms, as TNF-α <img>1031C (OR = 1.65 in Tunisia) and TNF-α <img>1211C (OR = 1.68 in Morocco), also presented significant associations, though less strong. These results demonstrate the existence of regional variations in genetic susceptibility to Behcet and the importance of population-specific studies. This is the first such review on the African continent and paves the way for further studies into the region's genetic determinants of the disease.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102368"},"PeriodicalIF":0.9,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145412789","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":"Molecular and in silico analysis of pamidronate disodium interaction with type IV osteogenesis imperfecta caused by the ultra-rare COL1A1 Variant rs72656337 (c.3664G>T; p.Ala1222Ser)","authors":"Maryam Dhary Kamel","doi":"10.1016/j.genrep.2025.102367","DOIUrl":"10.1016/j.genrep.2025.102367","url":null,"abstract":"<div><div>Type IV osteogenesis imperfecta (OI) is classically associated with heterozygous variants in COL1A1, the gene encoding the α1-chain of type I collagen. Here we explore whether an ultra-rare missense change located in the collagen C-terminal pro-peptide—rs72656337 (NM_000088.4:c.3664G &gt; T; p.Ala1222Ser, equivalent to p.Ala26Ser within exon 48)—could influence the molecular interaction between collagen and pamidronate disodium, a nitrogen-containing bisphosphonate routinely administered to children with type IV OI. All COL1A1 coding single-nucleotide variants were mined from dbSNP-156, filtered for C-terminal location and rarity (allele frequency &lt; 4 × 10⁻⁶ in gnomAD v4), yielding rs72656337 as the sole candidate for structural analysis. Using an in silico approach, examined the structural impact of the rs72656337 variant on the Collagen alpha-1(I) chain, focusing on how it affects protein conformation. Molecular docking in MOE placed pamidronate in a mixed acidic–basic pocket of the C-terminal region with a top docking score of −8.07 kcal mol⁻¹, forming hydrogen bonds to Asp59 (chain C) and Arg28 (chain B). Although direct collagen–pamidronate binding has not been demonstrated experimentally, our in-silico findings provide a testable framework for future biochemical assays and genotype-stratified studies in OI. As a hypothesis-generating study, our work motivates experimental validation (e.g., SPR/ITC with recombinant pro-peptides, hydroxyapatite-coated binding assays) and genotype-stratified clinical analyses to test whether C-terminal COL1A1 variants modify bisphosphonate efficacy in OI.</div></div>","PeriodicalId":12673,"journal":{"name":"Gene Reports","volume":"41 ","pages":"Article 102367"},"PeriodicalIF":0.9,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145525828","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}