Clinical biochemistry最新文献

{"title":"Cardiac function impairment in recipient twins of twin-to-twin transfusion syndrome: Insights from NT-proBNP levels in amniotic fluid","authors":"Wenyan Jian ,&nbsp;Dewei Guo ,&nbsp;Ruojin Yao ,&nbsp;Mi Pei ,&nbsp;Manhui Guo ,&nbsp;Fang Yang","doi":"10.1016/j.clinbiochem.2025.110894","DOIUrl":"10.1016/j.clinbiochem.2025.110894","url":null,"abstract":"<div><h3>Objectives</h3><div>To investigate changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in the amniotic fluid of recipient twins with twin-twin transfusion syndrome (TTTS), analyze the correlation between NT-proBNP and cardiac linear measurements, and assess the feasibility of NT-proBNP as a biochemical marker for fetal cardiac function.</div></div><div><h3>Design and methods</h3><div>A total of 47 pregnancies with TTTS, 21 idiopathic polyhydramnios pregnancies, and 114 normal singleton pregnancies were included from Xiangya Hospital of Central South University between October 2020 and July 2023. Fetal cardiac linear parameters, amniotic fluid depth, and NT-proBNP levels in amniotic fluid were measured across the three groups. The correlation of NT-proBNP with amniotic fluid depth, cardiac linear parameters, and CHOP score in TTTS recipients was analyzed.</div></div><div><h3>Results</h3><div>There was no statistically significant difference in amniotic fluid NT-proBNP levels and cardiac linear parameters between idiopathic polyhydramnios and normal singletons. However, NT-proBNP levels and cardiac parameters in TTTS recipient twins were significantly higher than in the other two groups (p &lt; 0.05). After adjusting for gestational variables, NT-proBNP levels in TTTS recipients showed significant correlations with atrial and ventricular diameters, ventricular wall thickness, cardiothoracic ratio, and CHOP score.</div></div><div><h3>Conclusions</h3><div>Amniotic fluid NT-proBNP is a sensitive and objective biochemical marker for assessing fetal cardiac function, independent of amniotic fluid volume. It serves as a valuable complement to echocardiographic assessment in evaluating the severity of fetal heart failure in TTTS recipients.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"136 ","pages":"Article 110894"},"PeriodicalIF":2.5,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolism of Natriuretic peptides and impact on insulin resistance and fat mass in healthy subjects","authors":"Timothy C.R. Prickett ,&nbsp;Lynley K. Lewis ,&nbsp;John F. Pearson ,&nbsp;Eric A. Espiner","doi":"10.1016/j.clinbiochem.2025.110893","DOIUrl":"10.1016/j.clinbiochem.2025.110893","url":null,"abstract":"<div><h3>Background</h3><div>Natriuretic peptides (NP) have important roles in regulating fat balance and metabolic health. Reduced concentrations of ANP and BNP in plasma are associated with increased insulin resistance in obesity. Whether this is due to increased clearance or reduced bioactivity of immunoreactive NP forms is unclear.</div></div><div><h3>Design and Method</h3><div>These questions were addressed in a community study of mildly obese subjects at middle age. The ratio of amino-terminal (NT) pro-NP to bioactive C-terminal NP was used as a putative index of the clearance of bioactive forms.</div></div><div><h3>Results</h3><div>Lower ratios of amino-terminal pro-NP to bioactive C-terminal NP were associated with increased insulin resistance. In linear regression models, NT-proANP and NT-proBNP outperformed ANP and BNP in predicting insulin resistance. Pro-NP glycosylation, which can impair NP and NT-proNP production in obesity, does not account for the diminished impact of ANP or BNP. Plasma concentrations of osteocrin, which competes for the NP clearance receptor (NPR-C) and potentially enhances NP bioactivity, was not associated with NPs, but did positively predict insulin resistance in females.</div></div><div><h3>Conclusions</h3><div>We find no evidence that increased clearance/degradation of NPs contributes to insulin resistance. Among the nine NP variants assessed, only NT-proANP and NT-proBNP independently predicted insulin resistance in both sexes. The impact of CNP on fat mass or insulin resistance was minor but significant in females. Lower concentrations of immunoreactive plasma ANP and BNP remains unexplained and requires closer study.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"136 ","pages":"Article 110893"},"PeriodicalIF":2.5,"publicationDate":"2025-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143349987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantitative abnormalities in the β-region of the electrophoretic profile of serum proteins as predictive markers of monoclonality: Machine learning for monoclonality prediction","authors":"Sara Cherkaoui,&nbsp;Slavka Penickova ,&nbsp;Frederic Cotton","doi":"10.1016/j.clinbiochem.2025.110892","DOIUrl":"10.1016/j.clinbiochem.2025.110892","url":null,"abstract":"<div><h3>Objective of the study</h3><div>To develop a machine learning algorithm aimed at predicting the presence of a monoclonal (M-) protein when the β-globulin fraction is elevated.</div></div><div><h3>Materials and method</h3><div>Patients were selected as part of the University Hospital Laboratory of Brussels routine diagnostic procedures from October 2021 to April 2022. Adult patients with serum protein electrophoresis showing elevated β1 and/or β2 fractions were included. The selection was done following strict exclusion criteria such as acute inflammation, iron deficiency anemia signs or supposed liver disease. To construct a predictive model for prediction of positive immunofixation (IFE) for monoclonality, the following factors were used: age, sex, β1 and β2 concentration (g/L), total proteins (g/L), IgA, IgM, IgG values (g/L) and hypogammaglobulinemia. The dataset underwent a random split, divided into a foundational training set (80%, 247 samples) and a foundational test set (20%, 62 samples). The training sets were subjected to five different algorithms: logistic regression, decision tree, random forest, gradient boosting, and support vector.</div></div><div><h3>Results</h3><div>309 patients were selected; 149 exhibited a negative IFE and 160 a positive IFE for monoclonality. The evaluation of the five tested models demonstrated very good performance, the chosen model was Random Forest for its high sensitivity (85%) and area under the receiver operating characteristic curve (91%).</div></div><div><h3>Conclusion</h3><div>An accurate algorithm was achieved for predicting the presence of M protein when the β-globulin fraction is elevated which enables early and improved diagnosis of monoclonal gammopathy.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"136 ","pages":"Article 110892"},"PeriodicalIF":2.5,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative stress and obesity are associated with endothelial dysfunction and subclinical atherosclerosis in adolescents","authors":"Josiane Aparecida de Miranda ,&nbsp;Warlley Rosa Cunha ,&nbsp;Júlio César Moraes Lovisi ,&nbsp;Carla Márcia Moreira Lanna ,&nbsp;Lucas Cézar Pinheiro ,&nbsp;Riccardo Lacchini ,&nbsp;José Eduardo Tanus-Santos ,&nbsp;Vanessa de Almeida Belo","doi":"10.1016/j.clinbiochem.2025.110889","DOIUrl":"10.1016/j.clinbiochem.2025.110889","url":null,"abstract":"<div><h3>Objectives</h3><div>This study explores the relationship between obesity, endothelial dysfunction, and the critical role of oxidative stress biomarkers in subclinical atherosclerosis.</div></div><div><h3>Design &amp; methods</h3><div>The study included 114 adolescents aged 12–17 years from Juiz de Fora, Brazil, divided into 40 individuals with obesity and 74 controls. Physical and biochemical assessments were conducted, including measurements of Brachial Flow-Mediated Dilation (BFMD), Carotid Intima-Media Thickness (IMT), and oxidative biomarkers such as nitrite, nitrate, and 8-isoprostane. Multiple regression analyses were used to evaluate associations between obesity, oxidative biomarkers, and endothelial function.</div></div><div><h3>Results</h3><div>Adolescents with obesity exhibited significantly reduced BFMD at 60 s (5.44 ± 2.31 % vs. 7.82 ± 2.07 % in controls; p &lt; 0.05) and 90 s (5.27 ± 2.64 % vs. 7.93 ± 2.12 % in controls; p &lt; 0.05). IMT was significantly higher in the group with obesity for both the right carotid artery (0.054 ± 0.005 cm vs. 0.047 ± 0.004 cm in controls; p &lt; 0.05) and the left carotid artery (0.053 ± 0.005 cm vs. 0.047 ± 0.004 cm in controls; p &lt; 0.05). Additionally, 8-isoprostane levels were higher in adolescents with obesity (49.75 ± 22.62 pg/mL vs. 42.36 ± 17.35 pg/mL in controls; p &lt; 0.05), indicating increased oxidative stress. Nitrite levels were significantly lower in adolescents with obesity (42.98 ± 10.62 nM vs. 49.94 ± 17.71 nM in controls; p &lt; 0.05). Additionally, nitrate levels were inversely associated with IMT in both the right (p = 0.01) carotid arteries in the multiple linear regression analyses.</div></div><div><h3>Conclusions</h3><div>The study highlights the association between obesity and early vascular changes in adolescents, evidenced by reduced BFMD, increased IMT, and altered oxidative stress biomarkers.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"136 ","pages":"Article 110889"},"PeriodicalIF":2.5,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051649","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of an automated assay for eosinophil-derived neurotoxin in serum","authors":"Carley Karsten ,&nbsp;Theodore Stier ,&nbsp;Christina Wood-Wentz ,&nbsp;Carin Smith ,&nbsp;Yifei K. Yang ,&nbsp;Melissa Snyder","doi":"10.1016/j.clinbiochem.2025.110890","DOIUrl":"10.1016/j.clinbiochem.2025.110890","url":null,"abstract":"<div><h3>Introduction</h3><div>Eosinophil-derived neurotoxin (EDN) is a promising biomarker for eosinophil activation during inflammatory responses. Here we evaluate the analytical performance of an automated fluorescence enzyme immunoassay for EDN in serum and explore its relationship with eosinophil counts in both healthy participants and those with eosinophilic conditions.</div></div><div><h3>Materials and Methods</h3><div>Paired serum samples were collected from individuals for whom a complete blood count with differential was ordered. EDN was measured using the ImmunoCAP EDN Assay Kit (research use only, Phadia AB / provided by Thermo Fisher Scientific) and 40 samples were also measured using an ELISA kit (research use only, ALPCO).</div></div><div><h3>Results</h3><div>The analytical measurement range of the ImmunoCAP assay was 2.6–200 µg/L. The imprecision across different EDN concentrations was ≤ 7.0 %. Stability and preanalytical requirements were determined. To minimize ex vivo degranulation and false elevation of EDN levels, serum should be removed from the cell pellet immediately after centrifugation. There was strong correlation for EDN measurements between ImmunoCAP and the comparative ELISA (r = 0.974), although a significant bias was observed. A 95th percentile reference range in 180 presumed healthy adults was calculated at 101 µg/L. Overall EDN was significantly higher in serum from patients with elevated circulating eosinophil counts (median = 120.0; <em>P</em> &lt; 0.0001). However, individual patients may present with discordant presentation of eosinophil counts and EDN concentration.</div></div><div><h3>Conclusions</h3><div>Together these results demonstrate that the ImmunoCAP EDN Assay Kit can reliably measure EDN in serum and may be useful for the evaluation of patients with conditions associated with hypereosinophilia.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"136 ","pages":"Article 110890"},"PeriodicalIF":2.5,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the predictive value of elevated triglycerides, triglyceride-glucose index (TyG), and TG/HDL ratios for cardiovascular disease and mortality during 20 years of follow-up: Tehran lipid and glucose study","authors":"Shayesteh Khalili ,&nbsp;Atieh Amouzegar ,&nbsp;Seyed Sattar Dorost ,&nbsp;Fereidoun Azizi ,&nbsp;Aryan Salahi-Niri","doi":"10.1016/j.clinbiochem.2025.110891","DOIUrl":"10.1016/j.clinbiochem.2025.110891","url":null,"abstract":"<div><h3>Objectives</h3><div>Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality globally, influenced by a complex interplay of risk factors including lipid disorders and insulin resistance (IR). The triglyceride-glucose (TyG) index and the triglyceride to high-density lipoprotein cholesterol (TG/HDL) ratio have emerged as potential indicators for assessing cardiovascular risk. This study aimed to evaluate the predictive value of hypertriglyceridemia, the TyG index, and the TG/HDL ratio for mortality and CVD occurrence within an Iranian population.</div></div><div><h3>Design and methods</h3><div>Conducted within the Tehran Lipid and Glucose Study over 20 years, this research analyzed 7,117 participants to assess the association between these lipid biomarkers and CVD risk and mortality. Participants were stratified by their TyG and TG/HDL indices, with Cox proportional hazards models determining risk ratios across three adjusted models considering various demographic and clinical variables.</div></div><div><h3>Results</h3><div>The study found significant associations between elevated triglycerides, TyG, and TG/HDL levels with increased risks of mortality and CVD during the 20-year follow-up. Specifically, the hazard ratios for CVD events were notably significant in the second triglyceride group (150–250 mg/dL), with a hazard ratio of 1.36 (1.19–1.55) in both Model 1 and Model 2, and in the third group (250–400 mg/dL), with ratios of 1.88 (1.63–2.17) in Model 1, 1.90 (1.65–2.19) in Model 2, and 1.44 (1.24–1.67) in Model 3.</div></div><div><h3>Conclusion</h3><div>Hypertriglyceridemia, the TyG index, and the TG/HDL ratio are easily calculable and clinically relevant markers for cardiovascular risk assessment. Their integration into routine health evaluations could facilitate early detection and management of at-risk individuals, potentially reducing the incidence and impact of CVD within the community.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"136 ","pages":"Article 110891"},"PeriodicalIF":2.5,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utility of the combination of high fluorescence cells and tumor markers for the diagnosis of malignant pleural effusions","authors":"Elisa Nuez-Zaragoza ,&nbsp;Indira Bhambi-Blanco ,&nbsp;Mònica Vidal-Pla ,&nbsp;Isabel Aparicio-Calvente ,&nbsp;M. Rosa Escoda-Giralt ,&nbsp;Joana Gallardo-Campos ,&nbsp;Joan C. Ferreres ,&nbsp;Luis Frisancho ,&nbsp;Laia Mas-Maresma ,&nbsp;Patricia Aguilera-Fernández ,&nbsp;Sonia Marco-Continente ,&nbsp;Marina Sierra-Boada ,&nbsp;Pablo Andreu-Cobo ,&nbsp;Miquel Gallego ,&nbsp;Jaume Trapé ,&nbsp;Vicente Aguadero","doi":"10.1016/j.clinbiochem.2025.110888","DOIUrl":"10.1016/j.clinbiochem.2025.110888","url":null,"abstract":"<div><h3>Background</h3><div>New diagnostic tools have emerged to assist the traditional diagnosis of malignant pleural effusion (MPE), such as high fluorescence cells (HFc) and tumor markers (TMs), determined by clinical laboratory automated pleural fluid workup. This study aimed to evaluate the diagnostic ability of the combination of HFc and TMs for diagnosing MPE.</div></div><div><h3>Methods</h3><div>We recruited hospitalized patients with pleural effusion at Parc Taulí University Hospital. We collected and analyzed pleural fluid and serum samples in the clinical laboratory, and we sent a sample of pleural fluid to the Pathology Department for cytology workup. We determined the pleural fluid cell count by Sysmex XN-10 and assessed TMs (CEA, CA19.9, and CA15.3) using the ECLIA Cobas e801 Roche in both pleural fluid and serum samples. We established the final MPE diagnosis based on positive cytology and/or positive pleural biopsy. We classified patients based on these final diagnoses and conducted a comparison between variables, along with multivariate logistic regression.</div></div><div><h3>Results</h3><div>The study included 316 pleural effusions from 221 patients recruited. Multivariate logistic regression indicated the most significant predictor variables for MPE were CA15.3 in serum, CEA ratio, and HFc. We calculated two different models: one excluding HFc and one including it, with the latter displaying superior diagnostic ability (area under the curve 0.91). This model could identify 100 % of MPE cases with 30 % specificity at low cut-offs, and higher values could help identify 60 % of MPE cases with 100 % specificity.</div></div><div><h3>Conclusions</h3><div>Per our findings, this model has high diagnostic performance and could serve as a swift, automated, dependable, non-invasive tool for MPE detection.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"136 ","pages":"Article 110888"},"PeriodicalIF":2.5,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143028065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical significance of fecal Syndecan-2 gene methylation combined with blood tumor abnormal protein detection in the diagnosis of colorectal cancer and precancerous lesions","authors":"Xuanjun Liu ,&nbsp;Guowei Zhao ,&nbsp;Weixu Mao ,&nbsp;Qigang Li ,&nbsp;Juan Liao ,&nbsp;Gan He","doi":"10.1016/j.clinbiochem.2025.110887","DOIUrl":"10.1016/j.clinbiochem.2025.110887","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the clinical significance of fecal Syndecan-2 <em>(SDC2)</em> gene methylation combined with blood tumor abnormal protein (TAP) detection for the diagnosis of colorectal cancer (CRC) and its precancerous lesions.</div></div><div><h3>Methods</h3><div>A retrospective study was conducted to collect patients diagnosed with CRC or colorectal adenoma (Ade) from March 2020 to March 2023, and healthy people (Nor) without any gastrointestinal diseases during the same period as the control group. All participants underwent the fecal <em>SDC2</em> gene methylation test, blood TAP test and fecal occult blood test (FOBT). The differences in the positivity rates of each index were compared, receiver operator characteristic curves were plotted and the area under the curve (AUC) was calculated to evaluate the diagnostic effects of different testing methods on CRC and its precancerous lesions.</div></div><div><h3>Results</h3><div>A total of 146 individuals were included in the study, including 69 CRC patients, 47 patients with Ade and 30 healthy individuals. The results showed that, SDC2, TAP and the combined assay had high comprehensive diagnostic efficacy for the diagnosis of CRC, but there was no significant difference between the three methods in terms of AUC, sensitivity, and specificity. However, for Ade, the combined detection was statistically significant, with a high AUC (0.905), high sensitivity (95.7%), and high specificity (86.7%).</div></div><div><h3>Conclusion</h3><div>Fecal <em>SDC2</em> gene methylation combined with blood TAP detection is an effective noninvasive screening and diagnostic method to enhance the early detection and treatment of CRC precancerous lesions, such as Ade, thereby reducing the incidence and mortality of CRC.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"136 ","pages":"Article 110887"},"PeriodicalIF":2.5,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143000947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"43 G > T polymorphism in the sucrase-isomaltase gene in the Chinese population prevents the glucose-lowering effect of acarbose","authors":"Junyao Huang ,&nbsp;Yan Chen ,&nbsp;Maolian Zhong ,&nbsp;Yan Liu ,&nbsp;Xing Wang ,&nbsp;Wenqiang Xiong ,&nbsp;Xiaodan Chen ,&nbsp;Xiaoyi Yi ,&nbsp;Yuting Liu ,&nbsp;Hong Zhang","doi":"10.1016/j.clinbiochem.2025.110875","DOIUrl":"10.1016/j.clinbiochem.2025.110875","url":null,"abstract":"<div><h3>Background</h3><div>Acarbose is an α-glucosidase inhibitor widely used clinically for its significant hypoglycemic effect, albeit with inter-individual variations in response. The sucrase-isomaltase (SI) enzyme is the primary target of acarbose. This study aims to investigate the impact of genetic polymorphisms in the SI gene on the pharmacodynamics of acarbose.</div></div><div><h3>Methods</h3><div>The Illumina sequencing platform and variation-related databases were employed to analyze probable gene polymorphism sites of SI. Based on the SI polymorphism sites, Chinese subjects (n = 66) were categorized into the wild-type homozygous group (Group A) and the heterozygous variant group (Group B, SI 43 G &gt; T). The validated hexokinase method was utilized to determine glucose concentrations in participants’ serum samples. The differences in blood glucose concentration reduction and pharmacodynamic parameters peak concentration (C_max) and area under the curve (AUC_0-2h) after administering the same dose of acarbose were analyzed between the two groups of subjects.</div></div><div><h3>Results</h3><div>Our results showed that the mean changes in glucose C_max, AUC_0-2h, maximum increase, and maximum decrease in Group B were each lower by 67.66 %, 63.05 %, 53.17 %, and 50 % compared to Group A (all p &lt; 0.05).</div></div><div><h3>Conclusions</h3><div>These data suggested that genetic polymorphism of the SI gene can significantly influence the hypoglycemic efficacy of acarbose, and the polymorphism of SI is associated with individual differences in clinical treatment outcomes.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"136 ","pages":"Article 110875"},"PeriodicalIF":2.5,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KNG1 mutations (c.618 T > G and c.1165C > T) cause disruption of the Cys206-Cys218 disulfide bond and truncation of the D5 domain leading to hereditary high molecular weight kininogen deficiency","authors":"Xiaoying Lv ,&nbsp;Pingping Li ,&nbsp;Ying Gui ,&nbsp;Caili Qin ,&nbsp;Shan Huang ,&nbsp;Yunwei Qi ,&nbsp;Huaping Chen ,&nbsp;Fuyong Zhang","doi":"10.1016/j.clinbiochem.2025.110877","DOIUrl":"10.1016/j.clinbiochem.2025.110877","url":null,"abstract":"<div><h3>Background</h3><div>High molecular weight kininogen (HMWK), encoded by the kininogen-1 (KNG1) gene, is a multifunctional glycoprotein closely associated with the initiation of blood coagulation, tumor growth, and other pathological processes.</div></div><div><h3>Objective</h3><div>We conducted a study on the clinical phenotype, genetic mutations, and molecular pathogenesis of a female patient with uterine leiomyosarcoma, who presented with HMWK deficiency and an isolated prolonged activated partial thromboplastin time (APTT).</div></div><div><h3>Methods</h3><div>Clinical phenotyping was conducted through APTT mixing studies, quantitative assessments of intrinsic coagulation factor activities, antigen levels of HMWK, and thromboelastography. Genetic analysis revealed a novel mutation within the KNG1 gene. Subsequent bioinformatics analysis focused on the evolutionary conservation of regions flanking codons 618 and 1165 of the KNG1 gene, with an aim of predicting the mutation’s functional impact.</div></div><div><h3>Results</h3><div>Clinical phenotypic analysis indicated a severe deficiency of HMWK antigen levels in the patient, with levels below 1.0 % of normal. Genetic sequencing identified two mutation sites in the KNG1 gene: a novel missense mutation in exon 5, c.618 T &gt; G (p.Cys206Trp), which leads to disruption of the disulfide bond between Cys206 and Cys218, and a known nonsense mutation in exon 10, c.1165C &gt; T (p.Arg389X), resulting in truncation of the D5 domain in the HMWK protein and reducing its quantity. These two mutations collectively impact the activation of HMWK within the coagulation system.</div></div><div><h3>Conclusion</h3><div>The compound heterozygous mutations, c.618 T &gt; G (p.Cys206Trp) and c.1165C &gt; T (p.Arg389X), result in a loss of HMWK function, leading to a deficiency in the kinin system and consequently a significant prolongation of the APTT. These findings advance understanding of coagulation factor deficiencies and inform diagnostic and therapeutic approaches for HMWK deficiency, potentially enhancing clinical management strategies.</div></div>","PeriodicalId":10172,"journal":{"name":"Clinical biochemistry","volume":"136 ","pages":"Article 110877"},"PeriodicalIF":2.5,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969870","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}