المؤلفون: Shallak, Mariam, Alberio, Tiziana, Fasano, Mauro, Monti, Maria, Iacobucci, Ilaria, Ladet, Julien, Mortreux, Franck, Accolla, Roberto S, Forlani, Greta

المساهمون: Shallak, Mariam, Alberio, Tiziana, Fasano, Mauro, Monti, Maria, Iacobucci, Ilaria, Ladet, Julien, Mortreux, Franck, Accolla, Roberto S, Forlani, Greta

مصطلحات موضوعية: ATL, HBZ, HTLV-1, alternative splicing, interactome, protein network, Adult, Basic-Leucine Zipper Transcription Factor, DEAD-box RNA Helicase, Human, Retroviridae Protein, Viral Protein, Human T-lymphotropic virus 1, RNA Splicing

الوصف: Adult T-cell leukemia/lymphoma (ATL) is a T-cell lymphoproliferative neoplasm caused by the human T-cell leukemia virus type 1 (HTLV-1). Two viral proteins, Tax-1 and HBZ play important roles in HTLV-1 infectivity and in HTLV-1-associated pathologies by altering key pathways of cell homeostasis. However, the molecular mechanisms through which the two viral proteins, particularly HBZ, induce and/or sustain the oncogenic process are still largely elusive. Previous results suggested that HBZ interaction with nuclear factors may alter cell cycle and cell proliferation. To have a more complete picture of the HBZ interactions, we investigated in detail the endogenous HBZ interactome in leukemic cells by immunoprecipitating the HBZ-interacting complexes of ATL-2 leukemic cells, followed by tandem mass spectrometry analyses. RNA seq analysis was performed to decipher the differential gene expression and splicing modifications related to HTLV-1. Here we compared ATL-2 with MOLT-4, a non HTLV-1 derived leukemic T cell line and further compared with HBZ-induced modifications in an isogenic system composed by Jurkat T cells and stably HBZ transfected Jurkat derivatives. The endogenous HBZ interactome of ATL-2 cells identified 249 interactors covering three main clusters corresponding to protein families mainly involved in mRNA splicing, nonsense-mediated RNA decay (NMD) and JAK-STAT signaling pathway. Here we analyzed in detail the cluster involved in RNA splicing. RNAseq analysis showed that HBZ specifically altered the transcription of many genes, including crucial oncogenes, by affecting different splicing events. Consistently, the two RNA helicases, members of the RNA splicing family, DDX5 and its paralog DDX17, recently shown to be involved in alternative splicing of cellular genes after NF-κB activation by HTLV-1 Tax-1, interacted and partially co-localized with HBZ. For the first time, a complete picture of the endogenous HBZ interactome was elucidated. The wide interaction of HBZ with molecules involved in RNA ...

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000840830300001; volume:13; journal:FRONTIERS IN IMMUNOLOGY; https://hdl.handle.net/11588/899181Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85136031022; https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.939863/fullTest

الإتاحة: https://doi.org/10.3389/fimmu.2022.939863Test
https://hdl.handle.net/11588/899181Test

المؤلفون: Maio A. D., De Rosa A., Pelucchi S., Garofalo M., Marciano B., Nuzzo T., Gardoni F., Isidori A. M., Di Luca M., Errico F., De Bartolomeis A., Marcello E., Usiello A.

المساهمون: Maio, A. D., De Rosa, A., Pelucchi, S., Garofalo, M., Marciano, B., Nuzzo, T., Gardoni, F., Isidori, A. M., Di Luca, M., Errico, F., De Bartolomeis, A., Marcello, E., Usiello, A.

مصطلحات موضوعية: Alzheimer’s disease, Dendritic spine, Parkinson’s disease, Postsynaptic density, Schizophrenia, ADAM10 Protein, Adaptor Proteins, Signal Transducing, Adult, Aged, 80 and over, Alzheimer Disease, Amyloid Precursor Protein Secretase, Autopsy, Case-Control Studie, Discs Large Homolog 1 Protein, Dorsolateral Prefrontal Cortex, Female, Gene Expression Regulation, Hippocampu, Human, Male, Membrane Protein, Middle Aged, Parkinson Disease

الوصف: Schizophrenia (SCZ) is a mental illness characterized by aberrant synaptic plasticity and connectivity. A large bulk of evidence suggests genetic and functional links between postsynaptic abnormalities and SCZ. Here, we performed quantitative PCR and Western blotting analysis in the dorsolateral prefrontal cortex (DLPFC) and hippocampus of SCZ patients to investigate the mRNA and protein expression of three key spine shapers: the actin‐binding protein cyclase‐associated protein 2 (CAP2), the sheddase a disintegrin and metalloproteinase 10 (ADAM10), and the synapse-associated protein 97 (SAP97). Our analysis of the SCZ post‐mortem brain indicated increased DLG1 mRNA in DLPFC and decreased CAP2 mRNA in the hippocampus of SCZ patients, compared to non‐psychiatric control subjects, while the ADAM10 transcript was unaffected. Conversely, no differences in CAP2, SAP97, and ADAM10 protein levels were detected between SCZ and control individuals in both brain regions. To assess whether DLG1 and CAP2 transcript alterations were selective for SCZ, we also measured their expression in the superior frontal gyrus of patients affected by neurodegenerative disorders, like Parkinson’s and Alzheimer’s disease. Interestingly, also in Parkinson’s disease patients, we found a selective reduction of CAP2 mRNA levels relative to controls but unaltered protein levels. Taken together, we reported for the first time altered CAP2 expression in the brain of patients with psychiatric and neurological disorders, thus suggesting that aberrant expression of this gene may contribute to synaptic dysfunction in these neuropathologies.

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000759795600001; volume:23; issue:3; firstpage:1539; journal:INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; http://hdl.handle.net/11588/878727Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85123439633

الإتاحة: https://doi.org/10.3390/ijms23031539Test
http://hdl.handle.net/11588/878727Test

المؤلفون: De Filippi R., Morabito F., Santoro A., Tripepi G., D'Alo F., Rigacci L., Ricci F., Morelli E., Zinzani P. L., Pinto A.

المساهمون: De Filippi, R., Morabito, F., Santoro, A., Tripepi, G., D'Alo, F., Rigacci, L., Ricci, F., Morelli, E., Zinzani, P. L., Pinto, A.

مصطلحات موضوعية: Body mass index, Hodgkin lymphoma, Immune checkpoint inhibitor, Immune-related adverse event, Adolescent, Adult, Aged, 80 and over, Female, Human, Male, Middle Aged, Nivolumab, Programmed Cell Death 1 Receptor, Retrospective Studie, Young Adult, Antineoplastic Agents, Immunological, Hodgkin Disease

الوصف: Background: Overweight and obese patients with solid tumors receiving anti-programmed cell death-1 (PD-1)/PD-ligand-1(PD-L1) immune checkpoint inhibitors exhibit improved survival and higher risk of immune-related adverse events (irAEs) than those with a normal body mass index (BMI). In classic Hodgkin lymphoma (cHL), the impact of BMI on survival and immune-related toxicity is unknown. We evaluated for the first time associations of BMI with survival and irAEs in patients with relapsed/refractory (RR)-cHL undergoing PD-1 blockade. Methods: Data from a multicenter study on 133 patients treated with the anti-PD1 antibody nivolumab (July 2015–December 2016) were retrieved from a prospective database. Progression-free (PFS), overall survival (OS), incidence and severity of irAEs according to BMI categories were estimated by Kaplan–Meier method, landmark-analyses and Cox regressions. Results: Patients, mostly males (63%, n = 84) with a median age of 35 years (range, 15–82), advanced stage (75%), B symptoms (63%), bulky disease (24%), a median of 4 previous treatments (range, 1–9), received a median of 18 nivolumab doses (range, 1–57). No statistically significant differences across BMI subgroups emerged as to PFS, with 1-year rates of 67.1% for both normal weight (n = 66; 49.6%) and overweight (n = 31; 23.3%) patients. Underweight (n = 12; 9%) and obese (n = 24; 18%) patients had a 1-year PFS of 54.5% and 49%, respectively. In survival analyses, BMI either as a continuous (P = 0.5) or categorical (P for trend = 0.63) variable failed to associate with PFS. Response rates and time-to-response did not cluster in any BMI subset. No BMI-related differences in OS emerged across normal, overweight and obese patients but underweight patients had the worst survival. Occurrence of irAEs of whatever severity did not statistically associate with BMI. Conclusions: In patients with RR-cHL receiving nivolumab, no statistically significant differences emerged in response rates, PFS and OS across BMI categories of normal weight, ...

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000724767600001; volume:19; issue:1; firstpage:489; journal:JOURNAL OF TRANSLATIONAL MEDICINE; http://hdl.handle.net/11588/867234Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85120318131

الإتاحة: https://doi.org/10.1186/s12967-021-03134-4Test
http://hdl.handle.net/11588/867234Test

المؤلفون: Cutruzzola A., Irace C., Frazzetto M., Sabatino J., Gullace R., De Rosa S., Spaccarotella C., Concolino D., Indolfi C., Gnasso A.

المساهمون: Cutruzzola, A., Irace, C., Frazzetto, M., Sabatino, J., Gullace, R., De Rosa, S., Spaccarotella, C., Concolino, D., Indolfi, C., Gnasso, A.

مصطلحات موضوعية: Adolescent, Adult, Biomarker, Blood Viscosity, Cardiovascular Disease, Carotid Arterie, Female, Heart Function Test, Hemodynamic, Human, Male, Middle Aged, Neurofibromatosis 1, Young Adult, Disease Susceptibility

الوصف: Subjects with Neurofibromatosis 1 (NF1) develop vascular complications. The protein product of the gene affected in NF1, neurofibromin, physiologically modulates endothelial function and preserves vascular and myocardial structure. Our study aimed to verify whether subjects with NF1 have early, preclinical abnormalities of carotid artery structure, brachial artery function, and cardiac function. We recruited 22 NF1 subjects without previous cardiovascular events and 22 healthy control subjects. All subjects underwent measurement of carotid artery intima-media thickness (IMT), evaluation of brachial artery endothelial function after ischemia and exercise, and cardiac function. Mean IMT was 543 ± 115 μ in NF1 subjects and 487 ± 70 μ in Controls (p < 0.01). Endothelial function was significantly dumped in NF1 subjects. The dilation after ischemia and exercise was respectively 7.5(± 4.8)% and 6.7(± 3.0)% in NF1 versus 10.5(± 1.2)% and 10.5(± 2.1)% in control subjects (p < 0.02; p < 0.002). Left ventricular systolic function assessed by Global Longitudinal Strain was significantly different between NF1 subjects and Controls: − 19.3(± 1.7)% versus − 21.5(± 2.7)% (p < 0.008). These findings demonstrate that NF1 patients have early morphological and functional abnormalities of peripheral arteries and systolic cardiac impairment and suggest the need for a tight cardiovascular risk evaluation and primary prevention in subjects with NF1.

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000555518700041; volume:10; issue:1; firstpage:12070; journal:SCIENTIFIC REPORTS; http://hdl.handle.net/11588/878851Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85088302459

الإتاحة: https://doi.org/10.1038/s41598-020-68908-0Test
http://hdl.handle.net/11588/878851Test

المؤلفون: Creanza, Annalisa, Lupoli, Roberta, LEMBO, ERMINIA, TECCE, NICOLA, Della Pepa, Giuseppe, LOMBARDI, GIANLUCA, Riccardi, Gabriele, Di Bonito, Procolo, Capaldo, Brunella

المساهمون: Creanza, Annalisa, Lupoli, Roberta, Lembo, Erminia, Tecce, Nicola, Della Pepa, Giuseppe, Lombardi, Gianluca, Riccardi, Gabriele, Di Bonito, Procolo, Capaldo, Brunella

مصطلحات موضوعية: Celiac disease, Glomerular filtration rate, Glycemic control, Microvascular complication, Type 1 diabete, Adult, Case-Control Studie, Diabetes Mellitus, Type 1, Female, Human, Male, Internal Medicine, Endocrinology, Diabetes and Metabolism

الوصف: Aims: To investigate whether in type 1 diabetes (T1DM) patients the concomitance of long-lasting celiac disease (CD) treated with a gluten free diet (GFD) impacts glycaemic control and the prevalence/severity of microvascular complications. Methods: A case-control, observational study was performed in 34 patients with T1DM and GFD-treated CD and 66 patients with T1DM alone matched for age, gender, and T1DM duration. Anthropometric parameters, glucose control (HbA1c), status of chronic complications and concomitant autoimmune diseases were evaluated. Results: HbA1c level was similar in T1DM + CD and T1DM alone (7.8 ± 1.0 vs 7.7 ± 1.1%, P = 0.57); insulin requirement was significantly higher in T1DM + CD compared with T1DM (P = 0.04). There were no differences in systolic blood pressure while diastolic blood pressure was significantly lower in T1DM + CD (P = 0.003). The prevalence/severity of microvascular complications was similar between the two groups. Glomerular filtration rate (eGFR) was significantly lower in T1DM + CD (100 ± 20 vs 110 ± 16 ml/min/1.73 m2, P = 0.007). Conclusions: In patients with T1DM, the co-occurrence of long-term GFD-treated CD neither worsens glycemic control nor negatively impacts chronic microvascular complications. However, patients with T1DM + CD have lower eGFR values than those with T1DM alone.

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000445129900035; volume:143; firstpage:282; lastpage:287; numberofpages:6; journal:DIABETES RESEARCH AND CLINICAL PRACTICE; http://hdl.handle.net/11588/737351Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85051112495; www.elsevier.com/locate/diabres

الإتاحة: https://doi.org/10.1016/j.diabres.2018.07.031Test
http://hdl.handle.net/11588/737351Test

المؤلفون: Tecce, Nicola, Masulli, Maria, Palmisano, Luisa, Gianfrancesco, Salvatore, Piccolo, Roberto, Pacella, Daniela, Bozzetto, Lutgarda, Massimino, Elena, Della Pepa, Giuseppe, Lupoli, Roberta, Vaccaro, Olga, Riccardi, Gabriele, Capaldo, Brunella

المساهمون: Tecce, Nicola, Masulli, Maria, Palmisano, Luisa, Gianfrancesco, Salvatore, Piccolo, Roberto, Pacella, Daniela, Bozzetto, Lutgarda, Massimino, Elena, Della Pepa, Giuseppe, Lupoli, Roberta, Vaccaro, Olga, Riccardi, Gabriele, Capaldo, Brunella

مصطلحات موضوعية: 2019 ESC guideline, Cardiovascular disease, STENO Type 1 risk engine, Type 1 diabete, Adult, Human, Retrospective Studie, Risk Assessment, Risk Factor, Cardiology, Diabetes Mellitus, Type 1

الوصف: The study compares the performance of the European Society of Cardiology (ESC) risk criteria and the Steno Type 1 Risk Engine (ST1RE) in the prediction of cardiovascular (CV) events.

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000862757000004; volume:190; firstpage:110001; journal:DIABETES RESEARCH AND CLINICAL PRACTICE; https://hdl.handle.net/11588/901274Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85135076174

الإتاحة: https://doi.org/10.1016/j.diabres.2022.110001Test
https://hdl.handle.net/11588/901274Test

المؤلفون: Mayer, Ingrid A., Abramson, Vandana G., Formisano, Luigi, Balko, Justin M., Estrada, Mónica V., Sanders, Melinda E., Juric, Dejan, Solit, David, Berger, Michael F., Won, Helen H., Li, Yisheng, Cantley, Lewis C., Winer, Eric, Arteaga, Carlos L.

المساهمون: Mayer, Ingrid A., Abramson, Vandana G., Formisano, Luigi, Balko, Justin M., Estrada, Mónica V., Sanders, Melinda E., Juric, Dejan, Solit, David, Berger, Michael F., Won, Helen H., Li, Yisheng, Cantley, Lewis C., Winer, Eric, Arteaga, Carlos L.

مصطلحات موضوعية: Adult, Aged, Antineoplastic Combined Chemotherapy Protocol, Aromatase Inhibitor, Biomarkers, Tumor, Breast Neoplasm, Cell Line, DNA Mutational Analysi, Female, Human, In Situ Hybridization, Fluorescence, Maximum Tolerated Dose, Middle Aged, Mutation, Neoplasm Metastasi, Neoplasm Staging, Nitrile, Phosphatidylinositol 3-Kinase, Receptor, ErbB-2, Fibroblast Growth Factor, Type 1, Receptors, Estrogen, Thiazole, Treatment Outcome, Triazole, Oncology

الوصف: Purpose: Alpelisib, a selective oral inhibitor of the class I PI3K catalytic subunit p110α, has shown synergistic antitumor activity with endocrine therapy against ER+/PIK3CA-mutated breast cancer cells. This phase Ib study evaluated alpelisib plus letrozole's safety, tolerability, and preliminary activity in patients with metastatic ER+ breast cancer refractory to endocrine therapy. Experimental design: Twenty-six patients received letrozole and alpelisib daily. Outcomes were assessed by standard solid-tumor phase I methods. Tumor blocks were collected for DNA extraction and next-generation sequencing. Results: Alpelisib's maximum-tolerated dose (MTD) in combination with letrozole was 300 mg/d. Common drug-related adverse events included hyperglycemia, nausea, fatigue, diarrhea, and rash with dose-limiting toxicity occurring at 350 mg/d of alpelisib. The clinical benefit rate (lack of progression ≥6 months) was 35% (44% in patients with PIK3CA-mutated and 20% in PIK3CA wild-type tumors; 95% CI, 17%-56%), including five objective responses. Of eight patients remaining on treatment ≥12 months, six had tumors with a PIK3CA mutation. Among evaluable tumors, those with FGFR1/2 amplification and KRAS and TP53 mutations did not derive clinical benefit. Overexpression of FGFR1 in ER+/PIK3CA mutant breast cancer cells attenuated the response to alpelisib in vitro CONCLUSIONS: The combination of letrozole and alpelisib was safe, with reversible toxicities. Clinical activity was observed independently of PIK3CA mutation status, although clinical benefit was seen in a higher proportion of patients with PIK3CA-mutated tumors. Phase II and III trials of alpelisib and endocrine therapy in patients with ER+ breast cancer are ongoing.

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000393876300006; volume:23; issue:1; firstpage:26; lastpage:34; numberofpages:9; journal:CLINICAL CANCER RESEARCH; http://hdl.handle.net/11588/698508Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85010301206; http://clincancerres.aacrjournals.org/content/23Test/1/26.full-text.pdf

الإتاحة: https://doi.org/10.1158/1078-0432.CCR-16-0134Test
http://hdl.handle.net/11588/698508Test
http://clincancerres.aacrjournals.org/content/23Test/1/26.full-text.pdf

المؤلفون: Villani A., Potestio L., Fabbrocini G., Scalvenzi M.

المساهمون: Villani, A., Potestio, L., Fabbrocini, G., Scalvenzi, M.

مصطلحات موضوعية: Basal cell carcinoma, Cemiplimab, Hedgehog inhibitor, Sonidegib, Squamous cell carcinoma, Vismodegib, Adult, Hedgehog Protein, Human, Programmed Cell Death 1 Receptor, Carcinoma, Basal Cell, Squamous Cell, Skin Neoplasms

الوصف: Non-melanoma skin cancers, also known as keratinocyte tumors, have an increasing incidence worldwide, with basal cell carcinoma and squamous cell carcinoma being the most represented ones. Although surgery represents the gold-standard treatment for both tumors, some cases can progress to an advanced or a metastatic state and targeted therapy is required. Hedgehog signaling pathway has an important role in the development of basal cell carcinoma, and its inhibition is the key to new treatment options available for the treatment of locally advanced and metastatic basal cell carcinoma. Cutaneous squamous cell carcinoma is the second most frequent malignant skin cancer; when presenting in advanced or metastatic stage, alternative treatments are required; cemiplimab is a human monoclonal antibody directed against programmed cell death-1 receptor that acts by blocking T-cell inactivation and is the first drug approved for the treatment of adult patients with metastatic or locally advanced cutaneous squamous cell carcinoma. Studies evaluating pembrolizumab, ipilimumab and nivolumab as alternative treatments for advanced squamous cell carcinoma are still underway. Objective of this review is to analyze and discuss the novel therapies for advanced basal cell carcinoma and squamous cell carcinoma to obtain a sharper perspective of the available treatment options.

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000749170300001; volume:39; issue:3; firstpage:1164; lastpage:1178; numberofpages:15; journal:ADVANCES IN THERAPY; http://hdl.handle.net/11588/884067Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85123863336

الإتاحة: https://doi.org/10.1007/s12325-022-02044Test-1
http://hdl.handle.net/11588/884067Test

المؤلفون: Immacolata, Cozzolino, Valeria, Varone, PICARDI, MARCO, Carlo, Baldi, Domenico, Memoli, Giuseppe, Ciancia, Carmine, Selleri, DE ROSA, GAETANO, VETRANI, ANTONIO, Pio, Zeppa

المساهمون: Immacolata, Cozzolino, Valeria, Varone, Picardi, Marco, Carlo, Baldi, Domenico, Memoli, Giuseppe, Ciancia, Carmine, Selleri, DE ROSA, Gaetano, Vetrani, Antonio, Pio, Zeppa

مصطلحات موضوعية: B-cell lymphoma 6 (BCL6), CD10, cell block, diffuse large B-cell lymphoma (DLBCL), fine-needle aspiration (FNA), multiple myeloma oncogene 1 (MUM1), non-Hodgkin lymphoma, Adult, Aged, 80 and over, Biopsy, Fine-Needle, Cohort Studie, DNA-Binding Protein, Female, Gene Expression Profiling, Human, Immunohistochemistry, Interferon Regulatory Factor, Linear Model, Lymphoma, Large B-Cell, Diffuse, Male, Middle Aged, Neprilysin, Prognosi, Prospective Studie, Gene Expression Regulation, Neoplastic

الوصف: BACKGROUND: Gene expression profiling has divided diffuse large B-cell lymphoma (DLBCL) into 2 main subgroups: germinal center B (GCB) and non-GCB type. This classification is reproducible by immunohistochemistry using specific antibodies such as CD10, B-cell lymphoma 6 (BCL6), and multiple myeloma oncogene 1 (MUM1). Fine-needle aspiration (FNA) plays an important role in the diagnosis of non-Hodgkin lymphoma, and in some cases FNA may be the only available pathological specimen. The objectives of the current study were to evaluate CD10, BCL6, and MUM1 immunostaining on FNA samples by testing the CD10, BCL6, and MUM1 algorithm on both FNA cell blocks (CB) and conventional smears (CS), evaluating differences in CB and CS immunocytochemical (ICC) performance, and comparing results with histological data. METHODS: Thirty-eight consecutive DLBCL cases diagnosed by FNA were studied. Additional passes were used to prepare CB in 22 cases and CS in 16 cases; the corresponding sections and smears were immunostained using CD10, BCL6, and MUM1 in all cases. The data obtained were compared with histological immunostaining in 24 cases. RESULTS: ICC was successful in 33 cases (18 CB and 15 CS) and not evaluable in 5 cases (4 CB and 1 CS). The CD10-BCL6-MUM1 algorithm subclassified DLBCL as GCB (9 cases) and non-GCB (24 cases). ICC data were confirmed on histologic staining in 24 cases. CONCLUSIONS: CD10, BCL6, and MUM1 ICC staining can be performed on FNA samples. The results herein prove it is reliable both on CB and CS, and is equally effective and comparable to immunohistochemistry data.

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000370737500008; volume:124; issue:2; firstpage:135; lastpage:143; numberofpages:9; journal:CANCER CYTOPATHOLOGY; http://hdl.handle.net/11588/642122Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84958818313; http://onlinelibrary.wiley.com/journal/10.1002Test/(ISSN)1934-6638

الإتاحة: https://doi.org/10.1002/cncy.21626Test
http://hdl.handle.net/11588/642122Test

المؤلفون: Di Taranto MD, Staiano A, D'AGOSTINO, MARIA NICOLETTA, D'Angelo A, Bloise E, Morgante A, MAROTTA, GENNARO, Gentile M, RUBBA, PAOLO OSVALDO FEDERICO, FORTUNATO, GIULIANA

المساهمون: DI TARANTO, MARIA DONATA, Staiano, A, D'Agostino, MARIA NICOLETTA, D'Angelo, A, Bloise, E, Morgante, A, Marotta, Gennaro, Gentile, M, Rubba, PAOLO OSVALDO FEDERICO, Fortunato, Giuliana

مصطلحات موضوعية: Apolipoprotein A-V (APOA5), Familial combined hyperlipidemia, Single nucleotide polymorphism (SNP), Upstream stimulatory factor 1 (USF1), Adult, Apolipoprotein A-V, Apolipoproteins A, Body Mass Index, Case-Control Studie, European Continental Ancestry Group, Female, Genetic Association Studie, Genetic Predisposition to Disease, Human, Hyperlipidemia, Familial Combined, Italy, Male, Middle Aged, Polymorphism, Single Nucleotide, Triglyceride, Upstream Stimulatory Factor, Molecular Biology, Cell Biology

الوصف: Familial combined hyperlipidemia (FCH) is a polygenic and multifactorial disease characterized by a variable phenotype showing increased levels of triglycerides and/or cholesterol. The aim of this study was to identify single nucleotides (SNPs) in lipid-related genes associated with FCH. METHODS AND RESULTS: Twenty SNPs in lipid-related genes were studied in 142 control subjects and 165 FCH patients after excluding patients with mutations in the LDLR gene and patients with the E2/E2 genotype of APOE. In particular, we studied the 9996G > A (rs2073658) and 11235C > T (rs3737787) variants in the Upstream Stimulatory Factor 1 gene (USF1), and the -1131T > C (rs662799) and S19W (rs3135506) variants in the Apolipoprotein A-V gene (APOA5). We found that the frequencies of these variants differed between patients and controls and that are associated with different lipid profiles. At multivariate logistic regression SNP S19W in APOA5 remained significantly associated with FCH independently of age, sex, BMI, cholesterol and triglycerides. CONCLUSIONS: Our results show that the USF1 and APOA5 polymorphisms are associated with FCH and that the S19W SNP in the APOA5 gene is associated to the disease independently of total cholesterol, triglycerides and BMI. However, more extensive studies including other SNPs such as rs2516839 in USF1, are required.

العلاقة: info:eu-repo/semantics/altIdentifier/wos/WOS:000350532300004; volume:29; issue:1; firstpage:19; lastpage:24; numberofpages:6; journal:MOLECULAR AND CELLULAR PROBES; http://hdl.handle.net/11588/595943Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-84923359745; http://www.elsevier.com/inca/publications/store/6/2/2/9Test/1/8/index.htt

الإتاحة: https://doi.org/10.1016/j.mcp.2014.10.002Test
http://hdl.handle.net/11588/595943Test
http://www.elsevier.com/inca/publications/store/6/2/2/9Test/1/8/index.htt