Genetic testing and molecular biomarkers最新文献

{"title":"Enhancing Genotype-Phenotype Correlation in Pediatric PKU: A Comparative Analysis of Hotspot Mutations and Prediction Models Across 12 Chinese Regions.","authors":"Li Zhang, Jie Ren, Jilong Su, Wenjuan Kang, Ke Dai, Xinhua Zhang, Hanzhou Guan","doi":"10.1177/19450265261440180","DOIUrl":"10.1177/19450265261440180","url":null,"abstract":"<p><strong>Objective: </strong>Phenylketonuria (PKU) is a genetic metabolic disorder caused by mutations in the phenylalanine hydroxylase (<i>PAH</i>) gene, with an incidence rate in China of approximately 1 in 11,000. PKU exhibits high heterogeneity, making the study of genotype-phenotype correlations essential for effective diagnosis and treatment.</p><p><strong>Methods: </strong>This study aimed to analyze the genotype-phenotype correlation in pediatric PKU patients in China, with a special focus on hotspot mutations across different regions.We compared the accuracy of two prediction models: the allele phenotype value/genotype-phenotype value system and the prediction system based on the sum of assigning value (AV) scores from PAH activity, evaluating both models based on available patient data from various regions.</p><p><strong>Results: </strong>The majority of genotypes in PKU patients were found to be compound heterozygotes. Classical PKU patients (cPKU) accounted for the highest proportion (44%), while the percentage of patients with mild hyperphenylalaninemia was relatively low at 22%. Among the eight regions studied, the APV/GPV system demonstrated higher accuracy (72.02%) compared with the AV score prediction system (56.82%, <i>p</i> < 0.05); however, for the cPKU phenotype alone, the difference in accuracy was not significant (<i>p</i> > 0.05).</p><p><strong>Discussion: </strong>This study provides insights into the relationship between genotypes and phenotypes in PKU patients across different regions of China, emphasizing the importance of analyzing hotspot mutations for understanding genotype-phenotype correlations. The findings highlight the need to enhance hotspot mutation spectra for PKU patients and advocate for the development of more accurate prediction models, which can offer better protection for PKU patients and alleviate the burden on patients and their families.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"191-199"},"PeriodicalIF":1.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148435955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Glutathione S-Transferase (GST) Gene Polymorphisms and Coronary Artery Disease: A Case-Control Study in Bangladesh.","authors":"Sauda Sumaya Dina, Somzida Akter Moni, Faisal Abdullah Emon, Rajib Das, C M Shaheen Kabir, Md Abdul Muhit, Nahid Sharmin, Sheikh Zahir Raihan","doi":"10.1177/19450265261469737","DOIUrl":"10.1177/19450265261469737","url":null,"abstract":"<p><strong>Background: </strong>Glutathione-S-transferases (GSTs) play an important role in the detoxification and neutralization of oxidative stress products and xenobiotic compounds. Due to genetic polymorphisms in GST genes, GSTs partially or completely lose enzymatic activity, which may increase susceptibility to cardiovascular diseases. The objective of this study was to investigate hitherto unknown <i>GSTM1</i> and <i>GSTT1</i> null genotype frequencies in patients with coronary artery disease (CAD) and their potential association with CAD in the Bangladeshi population.</p><p><strong>Materials and methods: </strong>This study included 85 patients with CAD and 56 healthy control subjects confirmed by angiogram. Clinical parameters including triglyceride (TG), cholesterol, low-density lipoprotein (LDL), and high-density lipoprotein levels were also evaluated. Genotypes of the <i>GSTM1</i> and <i>GSTT1</i> genes were identified using polymerase chain reaction followed by 1.5% (W/V) agarose gel electrophoresis with subsequent detection on a UV transilluminator.</p><p><strong>Results: </strong>There were significant differences in the null genotype distribution of <i>GSTM1</i> and <i>GSTT1</i> alleles between controls and patients with CAD. A significant association of the null genotype with CAD susceptibility (<i>p</i> < 0.05) was also observed. The combination of <i>GSTM1</i> and <i>GSTT1</i> null genes potentially increases the risk of CAD (odds ratio = 6.208; 95% confidence interval; <i>p</i> < 0.05). TG, LDL, and serum cholesterol levels were higher in patients with CAD (<i>p</i> < 0.05). <i>GSTM1</i> and <i>GSTT1</i> null genetic variations may be associated with increased susceptibility to CAD in the Bangladeshi population.</p><p><strong>Conclusion: </strong>These findings suggest a potential association between GST gene polymorphisms and CAD susceptibility; however, larger studies are required to provide more robust and generalizable evidence in the Bangladeshi population.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"200-207"},"PeriodicalIF":1.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148445630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Diversity of the ACE2 Gene and Susceptibility to COVID-19 in Morocco Population.","authors":"Nourdin Harich, Hamid Farhane, Soufiane Karchali, Majida Motrane, Fatima-Ezzahra Anaibar, Said Nassor Abeid, Omar Abidi, Abderraouf Hilali","doi":"10.1177/19450265261468935","DOIUrl":"10.1177/19450265261468935","url":null,"abstract":"<p><strong>Background: </strong>The COVID-19 was the most amazing pandemic of the early third millennium, with significant variability in infection rates across regions worldwide. Genetic factors, particularly the ACE2 gene, coding for a common receptor implicated in facilitating SARS-CoV-2 entry into human cells, could play a crucial role in susceptibility to infection. Our study aimed to analyze the allelic frequency of four SNPs in ACE2 gene (rs4646127, rs2074192, rs2285666, rs112171234) and evaluate their correlations with COVID-19 infection rates in four regional samples from Morocco.</p><p><strong>Methods: </strong>The total sample (<i>N</i> = 200) was obtained from: Rif (<i>n</i> = 50), Doukkala (<i>n</i> = 50), Ouarzazate (<i>n</i> = 49), and, Guelmim (<i>n</i> = 51). Genomic DNA was extracted using the GeneJET™ kit and genotyped by real-time PCR using TaqMan technology.</p><p><strong>Results: </strong>Analyses revealed significant spatial variations in the frequencies of alternative alleles of the studied SNPs, ranging from 0% to 74%. A significant positive correlation was observed between the frequency of alternative G allele of the rs4646127 and the infection rate variation (<i>r</i> = 0.96; <i>p</i> = 0.03; <i>n</i> = 4). Furthermore, significant differences reached 54.17% with worldwide populations (from North Africa, sub-Saharan Africa, Europe, Latino-America, East Asia, and South Asia) for the total SNP's comparisons.</p><p><strong>Conclusions: </strong>Our results suggest a significant positive correlation between the frequency of the alternative allele of the ACE2 gene polymorphism rs4646127 and COVID-19 regional infection rates in Morocco. This property could be exploited to consider this SNP as a potential biomarker for identifying at-risk groups. However, due to the limited number of regional samples, our results for all the analyzed SNPs remain exploratory and would require confirmation through larger-scale studies.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"208-217"},"PeriodicalIF":1.2,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148420568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ICF Syndrome in Chinese Children: Four Case Reports with Novel Mutations.","authors":"Yan Lei, Yanchun Wang, Xiaoning Liu, Li Li","doi":"10.1177/19450265261464229","DOIUrl":"10.1177/19450265261464229","url":null,"abstract":"<p><p>Immunodeficiency, centromeric instability, facial anomalies (ICF) syndrome is a rare autosomal recessive disorder characterized by immunodeficiency, centromeric instability, and facial dysmorphism. We report four Chinese pediatric patients with ICF syndrome diagnosed between 2018 and 2021. All patients presented with recurrent infections due to hypogammaglobulinemia. Whole-exome sequencing identified four novel mutations: CDCA7 c.695delC (p. Val233Ter), HELLS c.560T>G (p.L187W), ZBTB24 compound heterozygous (c.1228_1229delinsC and c.649_652del), and ZBTB24 homozygous (c.1208A>G, p.H403R). To our knowledge, this is the first report of CDCA7 p. Val233Ter and HELLS p.L187W mutations globally. These findings expand the mutational spectrum of ICF syndrome.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"183-189"},"PeriodicalIF":1.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148307751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estimates of European Ancestry in U.S. Hispanics Using <i>HFE</i> p.C282Y (c.845G>A; rs1800562), a Highly Informative Autosomal Marker.","authors":"James C Barton, J Clayborn Barton, Ronald T Acton","doi":"10.1177/19450265261464225","DOIUrl":"10.1177/19450265261464225","url":null,"abstract":"<p><strong>Background: </strong>We estimated European ancestry in U.S. Hispanics using <i>HFE</i> p.C282Y (c.845G > A; rs1800562), a highly informative autosomal marker of European ancestry.</p><p><strong>Methods: </strong>We tabulated published p.C282Y allele frequencies in U.S. Hispanic control/population region/city cohorts. We assumed that Hispanics inherited p.C282Y from European ancestors only. We defined European ancestry (<i>M</i>) of each cohort as the quotient of its published p.C282Y frequency by the published aggregate p.C282Y frequency in Iberian Spaniards. We compared the present average region/city values of <i>M</i> and the aggregate <i>M</i> with previous European ancestries of U.S. Hispanics estimated using multiple ancestry-informative markers (AIMs).</p><p><strong>Results: </strong>There were 14,472 Hispanics (nine region/city cohorts; aggregate p.C282Y frequency 0.0176 [509/28,944] [95% confidence interval: 0.0159, 0.0189]). There were 12,297 Spaniards (34 population/control cohorts; aggregate p.C282Y frequency 0.0291 (716/24,594) [0.0271, 0.0313]). Nine region/city estimates of <i>M</i> differed 2.6-fold: Alabama 1.0000, California/Irvine 0.5395, California/Oakland 0.6186; California/San Diego 0.9381; Connecticut 0.6873; District of Columbia 0.3883; Hawaii 0.6976; New York 0.4330; and Oregon 1.0000. The average of these nine region/city estimates of <i>M</i> was 0.7003. The aggregate estimate of <i>M</i> in the present 14,472 Hispanics was 0.6048 [0.5369, 0.6728]. The range of estimated European ancestries in 29,365 Hispanics in eight previous studies that used multiple AIMs was 0.502-0.683.</p><p><strong>Conclusions: </strong>European ancestry in U.S. Hispanics estimated using p.C282Y frequencies varies across regions/cities. The average nine region/city and aggregate European ancestry estimates in the present U.S. Hispanics are similar to those in eight previous studies that used multiple AIMs.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"176-182"},"PeriodicalIF":1.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148351712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expanding the Phenotypic Spectrum of Trafficking Protein Particle Complex Subunit 9-Related Intellectual Developmental Disorder: Prader-Willi-like Presentation in a Tunisian Family.","authors":"Maha Ben Jemaa, Haifa El Mabrouk, Mona Mahfood, Ichraf Kraawa, Aida Rouissi, Ilhem Turki, Moez Gribaa, Salma Najar, Abdelaziz Tlili, Dorra Hmida","doi":"10.1177/19450265261468940","DOIUrl":"10.1177/19450265261468940","url":null,"abstract":"<p><strong>Background: </strong>Intellectual Disability-Obesity-Brain Malformations-Facial Dysmorphism Syndrome (IDOB-FMD) is a rare genetic disorder characterized by moderate to severe intellectual disability, microcephaly, and brain abnormalities such as a thin corpus callosum, cerebellar hypoplasia, and cerebral white matter hypoplasia, often observed on MRI scans. Additional features include obesity and craniofacial dysmorphism. IDOB-FMD is inherited in an autosomal recessive manner, attributed to Trafficking Protein Particle Complex Subunit 9 (TRAPPC9) deficiency, with a prevalence of less than 1 in 1,000,000. This syndrome shares clinical similarities with Prader-Willi syndrome (PWS).</p><p><strong>Results: </strong>In our study, we conducted a clinical evaluation of two Tunisian siblings suspected of having Prader-Willi-like syndrome (PWLS) based on their clinical presentation. Whole-exome sequencing (WES) was employed to identify genetic variants associated with the phenotype. Variant interpretation and segregation analysis were performed to ascertain the pathogenicity of the identified variants. WES revealed a homozygous mutation in the <i>TRAPPC9</i> gene in both siblings. The variant was predicted to be pathogenic and segregated with the phenotype within the family. Clinical examination was consistent with PWLS, including intellectual disability, microcephaly, and dysmorphism.</p><p><strong>Conclusions: </strong>Our findings emphasize the importance of genetic testing in patients presenting with PWLS features, highlighting a <i>TRAPPC9</i> mutation that expands the known mutational spectrum. This study, the second investigation of PWLS in Tunisia, reports a pathogenic variant in the <i>TRAPPC9</i> gene underlying the observed phenotype in this family, offering valuable insights into clinical management and genetic counseling. Our identification of this variant not only reveals genetic heterogeneity but also prompts further research to elucidate the genotype-phenotype correlations and molecular mechanisms underlying <i>TRAPPC9</i>-related disorders.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"167-175"},"PeriodicalIF":1.2,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148404389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Key Genes and Clinical Feature Analyses of Epidermal Growth Factor Receptor Mutations in Lung Adenocarcinoma.","authors":"Dilimureti Niyaze, Alai Shalitana, Jun Guo, Wenjia Guo, Ailixiati Ainiwaer, Keming Xu, Xiaohong Sun, Waresijiang Yibulayin","doi":"10.1177/19450265261440400","DOIUrl":"10.1177/19450265261440400","url":null,"abstract":"<p><strong>Background: </strong>Lung adenocarcinoma (LUAD) is a prevalent and aggressive form of lung cancer, characterized by late-stage diagnosis, high metastatic potential, and recurrence. Epidermal growth factor receptor (EGFR) mutations are commonly observed in LUAD. However, other key genes associated with EGFR mutations in LUAD remain to be clarified. Therefore, this study aims to identify key genes associated with EGFR mutations in LUAD and explore their potential mechanisms.</p><p><strong>Methods: </strong>The Cancer Genome Atlas (TCGA)-LUAD and LUAD sequencing datasets were utilized to compare survival outcomes between EGFR-mutant and wild-type groups. Differentially expressed genes (DEGs) were identified by comparing these groups within TCGA-LUAD, followed by algorithmic analysis to pinpoint key genes. Prognostic analyses were integrated with clinical features, resulting in the construction and validation of a nomogram. Further investigations included gene set enrichment analysis, tumor mutational burden evaluation, immune checkpoint profiling, immune cell infiltration analysis, and drug sensitivity testing.</p><p><strong>Results: </strong>The EGFR-mutant group exhibited significantly reduced survival rates (<i>p</i> < 0.05); a total of 654 DEGs were identified between the EGFR-mutant group and the wild-type group. Key genes including Apolipoprotein B, C-reactive protein, kininogen 1, F2, and Alpha-2-HS-glycoprotein (AHSG) were predominantly involved in complement and coagulation cascades, ribosomal function, and cytochrome P450 metabolism. Both T and N stages were found to be independent prognostic factors and were incorporated into a highly predictive nomogram. Three immune cell types-neutrophils, activated CD4⁺ T cells-and five immune checkpoints were identified. Mutually exclusive and co-occurrence mutation analysis revealed a mutually exclusive relationship between Titin (TTN) and EGFR. Additionally, there were significant differences in the half-maximal inhibitory concentration values of 49 drugs between the mutant and wild groups.</p><p><strong>Conclusion: </strong>This study identified five key genes linked to EGFR mutations in LUAD and analyzed their clinical features, providing new perspectives for its prevention and treatment.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":"30 6","pages":"139-152"},"PeriodicalIF":1.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147981334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-HLA Genetic Polymorphisms of Interleukin-17 and Interleukin-23 Receptor in Behcet's Syndrome.","authors":"Serap Boz, Mustafa Boz, Pelin Unsal, Pamir Cerci, Turker Duman, Umit Olmez","doi":"10.1177/19450265261447151","DOIUrl":"10.1177/19450265261447151","url":null,"abstract":"<p><strong>Background: </strong>Behcet's syndrome (BS) was first described in 1937 as a triad of oral aphthae, genital ulceration, and ocular involvement. It is now recognized as a multisystemic vasculitis that can affect central nervous, gastrointestinal, and cardiovascular systems. Despite extensive research, the etiology of BS remains unclear, and genetic, viral, and environmental factors are thought to contribute to its pathogenesis.</p><p><strong>Objective: </strong>This study aimed to investigate the role of interleukin-17 (IL-17) and IL-23 receptor (IL-23R) gene polymorphisms in the etiology of BS and to evaluate their associations with disease activity and clinical features. The IL-23/IL-17 axis was selected due to its pivotal role in T cell-mediated inflammation and vasculitis, which are key pathogenic mechanisms in BS.</p><p><strong>Materials and methods: </strong>This study was conducted at the Ankara University Faculty of Medicine over a 1-year period. A total of 142 patients with BS aged ≥18 years and 140 healthy controls without known rheumatologic or immunological diseases were included. BS was diagnosed according to the International Study Group criteria for Behçet's disease. Disease activity was assessed using the BS Activity Scale, and patients were classified as having active or inactive disease. Genomic DNA was extracted from peripheral blood samples. IL-17 and IL-23R gene polymorphisms were analyzed using the polymerase chain reaction-restriction fragment length polymorphism method.</p><p><strong>Results: </strong>The IL-17 rs2275913 and rs763780 polymorphisms and the IL-23R rs11209032 polymorphism were evaluated. The frequency of the homozygous AA genotype of the rs11209032 was significantly higher in the BS group than in healthy controls (85.9% vs. 17.4%, <i>p</i> < 0.001). Carriage of the A allele was associated with a markedly increased risk of BS; after adjustment for age and sex, carriers had approximately 16-fold higher odds of disease (adjusted odds ratios [OR] = 16.32, 95% confidence intervals [CI]: 9.76-27.12, <i>p</i> < 0.001). No significant differences were observed between BS patients and controls for the IL-17 polymorphisms. Gene polymorphisms were not associated with specific clinical manifestations. However, in the IL-17 rs763780 polymorphism, inactive patients had a higher frequency of the TT genotype compared with the TC genotype (<i>p</i> = 0.03), suggesting a potential role in disease activity rather than susceptibility.</p><p><strong>Conclusion: </strong>These findings suggest that IL-17 and IL-23R-related pathways may contribute to the pathogenesis of BS. While the IL-17 variant may be associated with disease activity, the IL-23R rs11209032 polymorphisms show a strong association with disease susceptibility. However, larger studies are needed to confirm these findings and clarify their clinical relevance.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"153-158"},"PeriodicalIF":1.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147768966","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Basis of Atherosclerosis: The Role of PLAU Gene Polymorphism in Coronary Artery Disease.","authors":"Rıdvan Bora, Rojda Tanrıverdi, Şenay Balcı, Cemil Gülüm, Selman Aytimur, Ahmet Burak Keçeci, Oben Döven, Lülüfer Tamer, Burak Toprak","doi":"10.1177/19450265261447209","DOIUrl":"10.1177/19450265261447209","url":null,"abstract":"<p><strong>Background: </strong>Coronary artery disease (CAD) is a multifactorial disorder influenced by both environmental and genetic factors. The PLAU gene, which plays a key role in fibrinolysis, inflammation, and extracellular matrix remodeling, has been implicated in atherosclerotic plaque progression. However, the relationship between PLAU polymorphisms and different clinical manifestations of CAD remains insufficiently clarified.</p><p><strong>Aims: </strong>This study aimed to investigate the distribution of the PLAU rs2227564 polymorphism in patients with acute coronary syndrome (ACS), chronic coronary syndrome (CCS), and angiographically normal controls, and to evaluate its potential association with CAD susceptibility.</p><p><strong>Methods: </strong>A total of 196 participants (ACS: 66, CCS: 65, controls: 65) who underwent coronary angiography were prospectively enrolled. Genotyping of the PLAU rs2227564 polymorphism was performed using real-time polymerase chain reaction with the TaqMan SNP Genotyping Assay. Genotype and allele frequencies were compared among groups. Dominant, recessive, and allelic genetic models were analyzed, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated.</p><p><strong>Results: </strong>Overall genotype and allele distributions were similar across the study groups (<i>p</i> = 0.737). However, under the dominant genetic model (CT + TT vs. CC), carriers of at least one T allele showed significantly increased susceptibility to both ACS (OR: 6.84, 95% CI: 1.47-31.89, <i>p</i> = 0.009) and CCS (OR: 6.60, 95% CI: 1.43-30.48, <i>p</i> = 0.008) compared with controls. No significant associations were observed in the recessive or allelic models.</p><p><strong>Conclusion: </strong>Although the rs2227564 polymorphism was not independently associated with CAD based on the overall genotype distribution, the dominant model findings suggest that carrying at least one T allele may contribute to disease susceptibility in specific clinical and population contexts. These findings should be considered hypothesis-generating and require confirmation in larger multicenter studies with functional validation.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"159-166"},"PeriodicalIF":1.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating Alu Elements as Biomarkers for Radiation-Induced Toxicity in Cancer.","authors":"Mansi Patel, Charmi Jyotishi, Suresh Prajapati, Reeshu Gupta","doi":"10.1177/19450265261444622","DOIUrl":"10.1177/19450265261444622","url":null,"abstract":"<p><p>Radiation therapy is a key treatment for many cancers, but patient responses vary due to differences in genomic stability and DNA repair capacity. Increasing evidence highlights the role of Alu elements, the most abundant short interspersed nuclear elements in the human genome, as regulators of cellular stress responses. This review summarizes current knowledge on Alu biology, including their structure, retrotransposition, methylation, and expression, with a focus on their activation by ionizing radiation and their influence on DNA damage, repair pathways, gene regulation, and immune signaling. Radiation exposure has been shown to activate Alu elements, resulting in genomic destabilization, impaired repair, and pro-inflammatory responses. Consistent with this, Alu-associated mutations and microsatellite instability were observed at loci linked to key cancer genes (e.g., <i>TP53, BRCA2</i>), aligning with increased loss of heterozygosity and exon mutational burden. In addition, Alu hypomethylation further promotes microsatellite instability, recombination, defective repair, and is associated with therapeutic resistance. In parallel, circulating cell-free DNA fragments containing Alu sequences have also been correlated with delivered radiation dose and clinical toxicity, underscoring their potential as minimally invasive biomarkers. Taken together, these findings position Alu activation as both a mechanistic driver of radio-response heterogeneity and a minimally invasive biomarker for biodosimetry and toxicity risk stratification.</p>","PeriodicalId":12603,"journal":{"name":"Genetic testing and molecular biomarkers","volume":" ","pages":"124-132"},"PeriodicalIF":1.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}