Human Gene最新文献

{"title":"Developmental validation of NeoTyper autosomal STR kit","authors":"Sudhir Verma , Rajan Pal , Jagdish Kandpal , Ankit Singh Bhadauriya , Manas Pandey , Mitali Kushwaha , Shiv Mohan Singh , Supriya Singh","doi":"10.1016/j.humgen.2024.201348","DOIUrl":"10.1016/j.humgen.2024.201348","url":null,"abstract":"<div><h3>Background</h3><div>Short Tandem Repeats (STRs) are pivotal to efficient human DNA profiling. Including mini-STRs can further improve the assay's efficiency. The FBI's (Federal Bureau of Investigation) expanded Combined DNA Index System (CODIS) list contains twenty STRs for human identification. The NeoTyper Autosomal kit developed by Neom Scientific Solutions Pvt. Ltd. enables the amplification of 28 loci, which include markers from the expanded CODIS list, are National DNA Index System (NDIS) recommended markers, and comply with the NDIS recommended allelic range. In addition, the kit also includes 8 more markers including Penta D and Penta E. The NeoTyper Autosomal kit STR markers includes 14 mini-STR which makes it very effective for the human identification of the degraded samples like unidentified body remains.</div><div>This is a developmental validation study for NeoTyper, based on the listed Scientific Working Group on DNA Analysis Methods (SWGDAM) guidelines.</div></div><div><h3>Methodology</h3><div>We extracted the human genomic DNA from blood and FFPE (Formalin-Fixed Paraffin-Embedded) samples, and performed PCR amplification for the 28 loci using the developed kit, NeoTyper, which features a six-dye chemistry. The amplified products were run on 3500xL Genetic Analyzer. We used GeneMapper ID-X v.1.4 (Applied Biosystems) to analyse peak height and allele calling. Developmental validation parameters, including genetic characterization, analysis of sensitivity, female-male mixture, precision, and accuracy (repeatability and reproducibility), were investigated and analysed. Furthermore, intra- and inter-laboratory comparisons, as well as mini-STR analysis and validation were done.</div></div><div><h3>Results</h3><div>The developed NeoTyper Autosomal kit demonstrated 100 % sensitivity up to a DNA concentration of 62.5 pg, as measured by the number of alleles called. The assay also demonstrated good precision (measured in terms of standard deviation, SD ranging between 0.60 and 0.77) and reproducibility, with alleles called at 100 % accuracy. Furthermore, precision was high (measured as SD ranging from 0.50 to 0.66), with a 100 % accuracy. In 90.9 % of the samples (10 out of 11 female-male sample varied ratio), the mixture analysis revealed 100 % of the alleles being called. A comparative analysis of mini-STRs in GlobalFiler and NeoTyper Autosomal kit revealed a 100 % accuracy of the NeoTyper mini-STRs.</div></div><div><h3>Conclusion</h3><div>In conclusion, the NeoTyper Autosomal kit developed by Neom Scientific Solutions Pvt. Ltd. enables the amplification of 28 loci, which includes markers from expanded CODIS list; are NDIS accepted markers and comply with their recommended allelic range. The integration of mini-STRs in the kit demonstrates its efficacy and reliability, particularly when addressing the difficulties posed by degraded samples. This developmental validation study demonstrates consistent performance with high sensiti","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201348"},"PeriodicalIF":0.5,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536241","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":"Unravelling the protective effects of peptide isolated from marine sponge extract MS01 against SH-SY5Y cell line and its in-silico pharmacokinetic analysis","authors":"G.B. Priyadharshini,&nbsp;C. Jaynthy","doi":"10.1016/j.humgen.2024.201345","DOIUrl":"10.1016/j.humgen.2024.201345","url":null,"abstract":"<div><div>Parkinson's disease (PD) is characterised by developing postural instability, resting seizures, tremors, and a movement problem coupled with stiffness. All the available drugs can improve motor function considerably, but they can also have negative side effects, especially if the problem gets worse. The structure-activity relation was performed in the DISCOVERY STUDIO V2.5.5 pharmacophore model using the HypoGen algorithm for a training set of 15 compounds. Here, xenin peptide fits well with a least cost difference and a fit value of 10.46, indicating a favourable pharmacological characteristic. Therefore, we tried applying gene network analysis in cytoHubba to find the hub gene for PD in <em>Danio rerio</em> and <em>Homo sapiens</em>, as zebrafish and humans share many disease proteins and processes. Molecular docking studies for the hub gene polyubiquitin B from <em>Danio rerio</em> and Parkin from <em>Homo sapiens</em>, as well as the peptide xenin obtained from the marine sponge extract MS01 was performed. The peptide exhibits a substantial binding affinity with the receptor UBB through 8 and PRKN through 4 intermolecular hydrogen bonds in their bonded and non-bonded interactions, although it has little effect on the protein structure, according to simulation studies and dynamical free energy calculations. The protein structure has also been stabilised in terms of energy, secondary structure, and flexibility by the peptide binding. In addition to in-silico analysis the extract was tested in-vitro on SH-SY5Y cells for its effectiveness against ROS and cell viability, which proved its qualitative effect.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201345"},"PeriodicalIF":0.5,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142536240","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":"Identification of potential microRNAs involved in pathogenesis of venous thromboembolism (VTE): A meta analysis","authors":"Sunanda Arya,&nbsp;Rashi Khare,&nbsp;Iti Garg,&nbsp;Swati Srivastava","doi":"10.1016/j.humgen.2024.201346","DOIUrl":"10.1016/j.humgen.2024.201346","url":null,"abstract":"<div><h3>Objective</h3><div>MicroRNAs (MiRNAs) are master regulators of gene expression and have been suggested as potential diagnostic and therapeutic biomarkers in variety of complex diseases. Venous thromboembolism is a major cause of morbidity and mortality worldwide. Several miRNA expression studies have been conducted to identify miRNAs linked to VTE prognosis. These studies reveal that various miRNAs are significantly up-regulated and down-regulated in VTE patients in comparison to healthy controls. Present meta-analysis deliberate findings of such studies to identify most potential miRNA targets associated with VTE.</div></div><div><h3>Methodology</h3><div>Comprehensive literature review on Pubmed was conducted. Present analysis assessed 20 research article out of a total of 383 articles screened, based on inclusion and exclusion criteria. The up-regulated and down-regulated miRNAs obtained from selected research articles were subjected to meta-analysis. The differentially expressed miRNAs so obtained and were used for further bioinformatic analysis, including gene ontology and pathway analysis of their target genes, to study their potential involvement in VTE pathogenesis.</div></div><div><h3>Results</h3><div>Twenty articles selected for meta-analysis included a total of 808 patients. These included 26 up-regulated miRNAs and 11 down-regulated miRNAs. The meta-analysis based on Odds ratio suggested that one up-regulated miRNA (hsa-miR-1233-3p) and two down-regulated miRNAs (hsa-miR-103a-3p and hsa-miR-200c) returned significantly higher Odds compared to other miRNAs. Further bioinformatics analysis of their target genes revealed that these miRNAs target a large number of genes involved in cell adhesion, cell migration, endothelial activation and inflammation genes.</div></div><div><h3>Conclusions</h3><div>Three miRNAs, viz.; hsa-miR-1233-3p, hsa-miR-103a-3p and hsa-miR-200c may play a crucial role in VTE pathogenesis and has potential to serve as reliable diagnostic or therapeutic biomarkers for VTE.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201346"},"PeriodicalIF":0.5,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441005","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":"Validation of gene polymorphisms (rs2682818 and rs2043556) in has-miR-618 and has-miR-605 with the breast cancer susceptibility","authors":"Arvin Hassani,&nbsp;Saeid Ghorbian","doi":"10.1016/j.humgen.2024.201343","DOIUrl":"10.1016/j.humgen.2024.201343","url":null,"abstract":"<div><h3>Background</h3><div>Breast cancer (BC) is one of the most frequent types of cancer and the second leading cause of cancer-affiliate death among ladies. BC is a heterogeneous sickness that is impacted by environment and genetic elements. Diagnosis in the early stages impacts treatment and patient survival rate. miRNA can play a vital role in BC's early stages of tumorigenesis. Single nucleotide polymorphism (SNP) can cause changes in miRNA expression and function, which are related to the risk of several cancers.</div></div><div><h3>Aim</h3><div>The goal of this examination is to assess the affiliation among two has-miR-605 (rs2043556A &gt; G) and has-miR-618 (rs2682818 C &gt; A) gene polymorphisms with the risk of BC in the Iranian ladies.</div></div><div><h3>Methods</h3><div>Our case-control examination assessed two hundred whole blood samples of one hundred ladies with BC and one hundred healthy ladies. Hence, to assess the connection between the presence of SNP miRNA genes and the risk of BC, genotyping was done by the usage of the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, then the usage of the <em>Chi-square test</em> of SPSS software statistically analyzed the acquired result.</div></div><div><h3>Results</h3><div>Our findings confirmed a statistically substantial distinction within the genotype frequency of the has-miR-618 gene polymorphism among the groups (<em>P</em> = 0.043), whereas no statistically substantial distinction inside the genotype frequency of the has-miR-605 gene polymorphism among the control and case (<em>P</em> = 0.183). In addition, the allelic frequency of two polymorphisms, (rs2043556 A &gt; G) G allele (OR = 2.163, CI 95 % = 1.56–2.988, <em>P</em> = 0.022) and (rs2682818 C &gt; A) A allele (OR = 3.997, CI 95 % = 1.584–10.081, <em>P</em> = 0.002) substantially enhance the risk of BC.</div></div><div><h3>Conclusion</h3><div>The results show that the G allele of rs2043556 and the A allele of rs2682818 increase the risk of BC in the women population of East Azerbaijan province.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201343"},"PeriodicalIF":0.5,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142441008","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":"Investigate the association between genetic polymorphisms of ACE and ACE-2 with some biomarkers in Iraqi patients with COVID-19.","authors":"Ali H. Mahmood ,&nbsp;Salwa J. Al-Awadi ,&nbsp;Marwa M. Al-Attar ,&nbsp;Rusul A.A. Alshammary ,&nbsp;Riam Sabah Abood","doi":"10.1016/j.humgen.2024.201344","DOIUrl":"10.1016/j.humgen.2024.201344","url":null,"abstract":"<div><h3>Background</h3><div>The angiotensin-converting enzyme 2 (ACE2) receptor plays a critical role in mediating SARS-CoV-2 infection. Understanding the genetic factors influencing COVID-19 severity is crucial for developing effective treatment strategies. This study aimed to investigate the association between genetic polymorphism of the <em>ACE</em> gene, specifically the insertion/deletion (I/D) polymorphism in the promoter region, and clinical parameters in COVID-19 patients.</div></div><div><h3>Methods</h3><div>A case-control study was conducted with 225 participants from an Iraqi population. Blood samples were collected for hematological analysis and <em>ACE</em> genotyping. The association between <em>ACE</em> genotypes (DD, ID, II), demographic factors, and clinical parameters, including D-dimer, ferritin, lactate dehydrogenase (LDH), C-reactive protein (CRP), white blood cell (WBC) count, lymphocyte count, packed cell volume (PCV), red blood cell (RBC) count, hemoglobin (HB), and platelet count, was assessed.</div></div><div><h3>Results</h3><div>COVID-19 patients exhibited significant differences compared to controls regarding D-dimer, ferritin, LDH, CRP, WBC, lymphocytes, PCV, and RBC (<em>P</em> &lt; 0.05), while no significant differences were found for HB and platelet counts. The DD genotype was predominant (43.11 %), followed by ID (39.56 %) and II (17.33 %). Notably, a significant association was observed between D-dimer levels and ACE genotype (<em>P</em> &lt; 0.0001), with higher levels observed in individuals with the DD genotype. Additionally, a significant correlation was found between ACE genotype and sex (<em>P</em> = 0.0163). No significant association was observed between genotype and ICU admission or lung CT severity.</div></div><div><h3>Conclusion</h3><div>Our findings suggest a potential link between the <em>ACE</em> D/D genotype and elevated D-dimer levels in COVID-19 patients, indicating a potential role for <em>ACE</em> gene polymorphism in influencing disease severity. Further research is warranted to elucidate the underlying mechanisms and explore the potential for personalized treatment approaches based on <em>ACE</em> genotype.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201344"},"PeriodicalIF":0.5,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142418246","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":"KRT14 as a potential prognostic marker for metastasis in metaplastic breast carcinoma","authors":"Bhaskar Gogoi ,&nbsp;Benjamin Lalrinpuia ,&nbsp;Lalhmingliana ,&nbsp;Nachimuthu Senthil Kumar","doi":"10.1016/j.humgen.2024.201341","DOIUrl":"10.1016/j.humgen.2024.201341","url":null,"abstract":"<div><div>Metaplastic breast cancer (MBC) is an aggressive breast cancer subtype with poor prognosis. To elucidate underlying genomic aberrations driving MBC, we conducted integrated transcriptomic analyses of MBC tumors and basal breast cancer cell lines with various transitioning phases (xE = epithelial phase clone, xM = mesenchymal phase clone and xEM = Epithelial-mesenchymal clone). Differential gene expression analysis between MBC vs non-MBC samples as well as between epithelial-mesenchymal (xEM) transitioning cells vs parental cells revealed 12 commonly dysregulated genes intersected from both the datasets meditates pathways governing EMT, migration, proliferation and metastasis. Further investigation onto those genes based on multi-omics approaches that include survival analysis, correlated expression patterns and interactomics indicated KRT14 had a key role in promoting MBC aggression through Epithelial mesenchymal transition leading to metastasis. Moreover, NPR3 was found to be a possible link between KRT14 and EMT in metastasis. To our knowledge, this is the first evident gene expression study to investigate the potential association between the expression of KRT14 and NPR3 and metastasis in MBC, and their potential involvement in the epithelial-mesenchymal transition (EMT) process. These mechanistic and prognostic insights gained can lead to targeted therapeutics against this rare, refractory disease. Overall, this work highlights the effectiveness of integrated multi-omics in revealing gene expression pattern and predictive biomarkers for metaplastic breast cancer subtypes with poor prognosis.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201341"},"PeriodicalIF":0.5,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142418244","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":"Therapeutic prospects and challenges in the human genetic disorder hyperbiliverdinemia","authors":"Sakshi Singh ,&nbsp;Manish Dwivedi ,&nbsp;Aiswarya Pawar ,&nbsp;Mahima Kori ,&nbsp;Anuradha Yadav ,&nbsp;Paras Porwal","doi":"10.1016/j.humgen.2024.201342","DOIUrl":"10.1016/j.humgen.2024.201342","url":null,"abstract":"<div><div>The epidermis, sclera, urine, and other bodily fluids have a greenish tint in hyperbiliverdinemia, a rare hepatic condition. Increased biliverdin as a result of ineffective conversion to bilirubin is the known explanation behind the onset of this disorder. The conversion of the bile pigment biliverdin to bilirubin is catalyzed by the oxidoreductase enzyme biliverdin reductase IX-α. Based on a case study, the development of hyperbiliverdinemia is reportedly caused by a novel mutation in the gene (BVRA) that encodes the protein biliverdin reductase A (enzyme) paired with a decompensated liver. Those who have been affected do not seem to experience symptoms outside of obstructive cholestasis; sometimes it is accompanied by liver failure; however, in some reports, liver failure is the only symptom faced by the affected individual. According to case reports, green jaundice occasionally goes away once obstructive cholestasis becomes resolved. This review examines jaundice, including its etiology, symptoms, and concomitant disease processes, with a focus on hyperbiliverdinemia, popularly known as “green jaundice.” Significant information regarding the therapeutics and treatment of jaundice, such as that of phototherapy and exchange transfusion, has also been discussed. Currently, there is no specific treatment for hyperbiliverdinemia; however, treating the symptoms of this disease seems to improve the affected individual's condition.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201342"},"PeriodicalIF":0.5,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142418245","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":"Investigation of the association between polymorphisms in DNA repair enzymes and STEMI","authors":"Damla Raimoglou ,&nbsp;Murat Cimci ,&nbsp;Elif Citak ,&nbsp;Selin Unal ,&nbsp;Narmina Malikova ,&nbsp;Eser Durmaz ,&nbsp;Mehmet Guven","doi":"10.1016/j.humgen.2024.201340","DOIUrl":"10.1016/j.humgen.2024.201340","url":null,"abstract":"<div><div>STEMI (ST-elevation myocardial infarction), a condition in which DNA damage likely contributes to its pathogenesis, is among the most severe manifestations of coronary artery disease. There are very few publications in this field in the literature. In our study, we examined the association between four polymorphisms in repair enzymes (<em>LIG4 Thr9Ile</em>, <em>XRCC6 promoter C-57G</em>, <em>XPA -4A/G</em>, <em>OGG1 Ser326Cys</em>) involved in three distinct DNA repair mechanisms [NHEJ (non-homologous end joining)], NER (nucleotide excision repair), and BER (base excision repair), and their impact on the risk of STEMI. This study involved 185 patients diagnosed with STEMI and included 155 healthy controls. The genotyping of SNPs was conducted through the PCR-RFLP (Polymerase chain reaction-restriction fragment length polymorphism) method for the following variants: <em>XRCC6</em> (rs2267437), <em>XPA</em> (rs1800975), <em>LIG4 (</em>rs1805388), and <em>OGG1</em> (rs1052133). No significant differences were observed in the genotype distributions of the <em>XRCC6</em> and <em>OGG1</em> variations between the control and patient groups. On the other hand, our findings indicate that individuals carrying the mutant <em>G</em> allele for <em>XPA</em> polymorphism and the mutant <em>T</em> allele for <em>LIG4</em> polymorphism are susceptible to STEMI. Our findings demonstrate the significance of NHEJ and NER DNA repair processes in the pathogenesis of STEMI, as evidenced by the observed relationship between <em>LIG4</em> and <em>XPA</em> polymorphisms.</div></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201340"},"PeriodicalIF":0.5,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142318694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered expression of insulin-like growth factor 2 mRNA binding protein 2 is associated with periodontal disease- a case-control analysis","authors":"Deepika Burra Anand ,&nbsp;Jaiganesh Ramamurthy ,&nbsp;Balachander Kannan ,&nbsp;Vijayashree Priyadharsini Jayaseelan ,&nbsp;Paramasivam Arumugam","doi":"10.1016/j.humgen.2024.201338","DOIUrl":"10.1016/j.humgen.2024.201338","url":null,"abstract":"<div><h3>Background/Purpose</h3><p>Periodontitis has a multifactorial pathogenesis involving genetic and epigenetic factors. Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is an N6-methyladenosine (m6A) reader that enhances messenger RNA (mRNA) stability in an m6A-dependent manner. It is being considered as a potential target for treating inflammatory diseases. However, its role in periodontitis and its specific target genes affected by m6A modification are not yet well understood. This study aims to investigate the expression of IGF2BP2 and its potential involvement in periodontitis.</p></div><div><h3>Materials and methods</h3><p>Seventy participants were recruited, including 35 patients with periodontitis and 35 healthy controls. Clinical examination and radiography were performed to confirm a diagnosis of periodontitis. Gingival tissue samples were collected from each participant, and IGF2BP2 expression was measured using real-time PCR and western blotting. In addition, <em>in silico</em> tools were used to identify the IGF2BP2 network pathway and its functions.</p></div><div><h3>Results</h3><p>IGF2BP2 expression was significantly higher in the periodontitis group than in the healthy control group (<em>p</em> &lt; 0.0001). Functional enrichment analysis revealed that the IGF2BP2 pathway network plays a crucial role in periodontal pathogenesis. In addition, pro-inflammatory cytokines, including <em>IL-1β</em> and <em>IL-6</em>, were significantly increased in the periodontitis group (<em>p</em> &lt; 0.0001) and were positively correlated with IGF2BP2 expression and m6A methylation sites.</p></div><div><h3>Conclusion</h3><p>Our study demonstrated that increased IGF2BP2 expression is associated with periodontitis, which may regulate proinflammatory cytokine production in an m6A-dependent manner. Further functional studies are required to understand the mechanism of action of IGF2BP2 in periodontitis.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201338"},"PeriodicalIF":0.5,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142272947","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":"Role of GSTP1 functional polymorphisms in molecular pathogenesis of colorectal cancer","authors":"Sravanthi Malempati ,&nbsp;Neelam Agrawal ,&nbsp;Devalaraju Ravisankar ,&nbsp;Venkata Sai Rahul Trivedi Kothapalli ,&nbsp;Srinivasulu Cheemanapalli ,&nbsp;Raghava Rao Tamanam ,&nbsp;Suresh Govatati ,&nbsp;Pasupuleti Sreenivasa Rao","doi":"10.1016/j.humgen.2024.201335","DOIUrl":"10.1016/j.humgen.2024.201335","url":null,"abstract":"<div><p>Glutathione S-transferase P1 (GSTP1) plays a crucial role in the detoxification of harmful substances and cancer-causing agents. Single nucleotide polymorphisms (SNPs) in GSTP1 can affect its ability to catalyze reactions and detoxify, thereby influencing the risk of developing colorectal cancer (CRC). This study aimed to investigate the impact of functional SNPs (fSNPs) in GSTP1 on the risk of CRC, as well as their structural and functional consequences. We analyzed a total of 126 selected GSTP1 SNPs, including fSNPs <em>rs1695 A &gt; G</em> (I105V) and <em>rs1138272 C &gt; T</em> (A114V), in CRC patients (<em>n</em> = 103) and controls (<em>n</em> = 107) of south Indian origin using PCR-sequencing analysis with genomic DNA from blood samples. To assess the structural integrity of <em>GSTP1</em> fSNPs, we conducted in silico analysis using various tools such as Swiss PDB Viewer, pyMOL mutagenesis wizard, ProSA-Web, and Pdbsum. Additionally, we performed functional characterization of <em>GSTP1</em> fSNPs using cell and molecular biology techniques. Our findings revealed a significant association between the I105V fSNP and CRC risk, while the A114V fSNP did not show any significance. However, both fSNPs exhibited stronger linkage disequilibrium in patients compared to controls. In silico analysis indicated a loss of structural integrity and reduced electrostatic potential energy in the double mutant <em>GSTP1</em> (V105/V114) compared to the native (I105/A114) or single mutant (V105/A114 and I105/V114) forms. Furthermore, FHC cells transfected with the <em>GSTP1</em> I105V variant exhibited increased proliferation, invasion, and colony formation, along with decreased GST activity compared to carriers of the wild-type <em>GSTP1</em>. On the other hand, the <em>GSTP1</em> A114V variant did not show a significant effect. Interestingly, FHC cells transfected with the double mutant <em>GSTP1</em> variant (V105/V114) demonstrated synergistic and enhanced effects compared to the <em>GSTP1</em> I105V variant. Consistent with these findings, plasma GST activity was significantly lower in haplogroups carrying both fSNPs compared to haplogroups with single or no fSNPs. To summarize, our findings indicate that while <em>GSTP1</em> I105V alone contributes to the etiology of CRC, A114V does not; however, their combined presence has a more significant impact.</p></div>","PeriodicalId":29686,"journal":{"name":"Human Gene","volume":"42 ","pages":"Article 201335"},"PeriodicalIF":0.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142232621","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}