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7 results on '"Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA)"'

1. Hypercoagulability in critically ill patients with COVID 19, an observational prospective study

Author

Laure Calvet, François Thouy, Olivier Mascle, Anne-Françoise Sapin, Kévin Grapin, Jean Mathias Liteaudon, Bertrand Evrard, Benjamin Bonnet, Mireille Adda, Bertrand Souweine, Claire Dupuis, Service de Médecine Intensive et Réanimation [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, CHU Clermont-Ferrand, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Laboratoire Microorganismes : Génome et Environnement (LMGE), and Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)

Subjects
Multidisciplinary, Critical Illness, Thromboembolism, Humans, COVID-19, Thrombophilia, Prospective Studies, Blood Coagulation Disorders, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Hemostatics, Thrombelastography
Abstract

Objective COVID 19 is often associated with hypercoagulability and thromboembolic (TE) events. The aim of this study was to assess the characteristics of hypercoagulability and its relationship with new-onset TE events and the composite outcome of need for intubation and/or death in intensive care unit (ICU) patients admitted for COVID. Design Prospective observational study. Setting Monocentric, intensive care, University Hospital of Clermont Ferrand, France. Patients Patients admitted to intensive care from January 2020 to May 2021 for COVID-19 pneumonia. Interventions Standard hemostatic tests and rotational thromboelastometry (ROTEM) were performed on admission and on day 4. Hypercoagulability was defined by at least one of the following criteria: D-dimers > 3000 μg/dL, fibrinogen > 8 g/L, EXTEM CFT below the normal range, EXTEM A5, MCF, Li 60 above the normal range, and EXTEM G-score ((5000 x MCF) / (100-MCF)) ≥ 11 dyne/cm2. Measurements and main results Of the 133 patients included, 17 (12.7%) developed new-onset TE events, and 59 (44.3%) required intubation and/or died in the ICU. ROTEM was performed in 133 patients on day 1 and in 67 on day 4. Hypercoagulability was present on day 1 in 115 (86.4%) patients. None of the hypercoagulability indices were associated with subsequent new-onset TE events on days 1 and 4 nor with the need for intubation and/or ICU death. Hyperfibrinogenemia > 8g/dL, higher D-dimers and higher EXTEM Li 60 on day 4 were predictive of need for intubation and/or of ICU death. Conclusions Our study confirmed that most COVID-19 ICU patients have hypercoagulability on admission and almost all on day 4. Hyperfibrinogenemia or fibrinolysis shutdown on day 4 were associated with unfavorable outcome.

Published
2022

2. Diversity matters in wheat mixtures: A genomic survey of the impact of genetic diversity on the performance of 12 way durum wheat mixtures grown in two contrasted and controlled environments

Author

Pauline Alsabbagh, Laurène Gay, Michel Colombo, Germain Montazeaud, Morgane Ardisson, Aline Rocher, Vincent Allard, Jacques L. David, Amélioration génétique et adaptation des plantes méditerranéennes et tropicales (UMR AGAP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de Montpellier (UM), Université de Lausanne = University of Lausanne (UNIL), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL), Génétique Diversité et Ecophysiologie des Céréales (GDEC), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), and European Project: 727247,H2020,H2020-SFS-2016-2,SolACE(2017)

Subjects
[SDV.GEN.GPL]Life Sciences [q-bio]/Genetics/Plants genetics, [SDV.BV.AP]Life Sciences [q-bio]/Vegetal Biology/Plant breeding, Multidisciplinary, Quantitative Trait Loci, [SDV.SA.AGRO]Life Sciences [q-bio]/Agricultural sciences/Agronomy, Genetic Variation, Edible Grain, Environment, Controlled, Triticum, Ecosystem
Abstract

In ecology, an increase in genetic diversity within a community in natural ecosystems increases its productivity, while in evolutionary biology, kinship selection predicts that relatedness on social traits improves fitness. Varietal mixtures, where different genotypes are grown together, show contrasting results, especially for grain yield where both positive and negative effects of mixtures have been reported. To understand the effect of diversity on field performance, we grew 96 independent mixtures each composed with 12 durum wheat (Triticum turgidum ssp. durum Thell.) inbred lines, under two contrasting environmental conditions for water availability. Using dense genotyping, we imputed allelic frequencies and a genetic diversity index on more than 96000 loci for each mixture. We then analyzed the effect of genetic diversity on agronomic performance using a genome-wide approach. We explored the stress gradient hypothesis, which proposes that the greater the unfavourable conditions, the more beneficial the effect of diversity on mixture performance. We found that diversity on average had a negative effect on yield and its components while it was beneficial on grain weight. There was little support for the stress gradient theory. We discuss how to use genomic data to improve the assembly of varietal mixtures.

Published
2021

3. In vitro osteoblast activity is decreased by residues of chemicals used in the cleaning and viral inactivation process of bone allografts

Author

Guillaume Villatte, Roger Erivan, Stéphane Descamps, Pierre Arque, Stéphane Boisgard, Yohann Wittrant, Service d’Orthopédie Traumatologie [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Institut de Chimie de Clermont-Ferrand (ICCF), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Unité de Nutrition Humaine (UNH), and Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA)

Subjects
Bone Transplantation, Osteoblasts, Multidisciplinary, [SDV]Life Sciences [q-bio], [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Carbon Dioxide, Alkaline Phosphatase, Allografts, Rats, Animals, Virus Inactivation, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Rats, Wistar, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

Allograft bone tissue has a long history of use. There are two main ways of preserving allografts: by cold (freezing), or at room temperature after an additional cleaning treatment using chemicals. These chemicals are considered potentially harmful to humans. The aim of the study was (i) to assess the presence of chemical residues on processed bone allografts and (ii) to compare the in vitro biocompatibility of such allografts with that of frozen allografts. The presence of chemical residues on industrially chemically treated bone was assessed by high performance liquid chromatography (HPLC) after extraction. Biocompatibility analysis was performed on primary osteoblast cultures from Wistar rats grown on bone disks, either frozen (F-bone group) or treated with supercritical carbon dioxide with no added chemical (scCO2-bone group) or industrially treated with chemicals (CT-bone group). Cell viability (XTT) was measured after one week of culture. Osteoblastic differentiation was assessed after 1, 7 and 14 days of culture by measuring alkaline phosphatase (ALP) activity directly on the bone discs and indirectly on the cell mat in the vicinity of the bone discs. Residues of all the chemicals used were found in the CT-bone group. There was no significant difference in cell viability between the three bone groups. Direct and indirect ALP activities were significantly lower (−40% to −80%) in the CT-bone group after 7 and 14 days of culture (p < 0.05). Residues of chemical substances used in the cleaning of bone allografts cause an in vitro decrease in their biocompatibility. Tissue cleaning processes must be developed that limit or replace these chemicals to favor biocompatibility.

Published
2022

4. Computer-assisted instruction versus inquiry-based learning: The importance of working memory capacity

Author

Chevalère, Johann, Cazenave, Loreleï, Berthon, Mickaël, Martinez, Ruben, Mazenod, Vincent, Borion, Marie-Claude, Pailler, Delphine, Rocher, Nicolas, Cadet, Rémi, Lenne, Catherine, Maïonchi-Pino, Norbert, Huguet, Pascal, Laboratoire de Psychologie Sociale et Cognitive (LAPSCO), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Laboratoire d'Informatique, de Modélisation et d'Optimisation des Systèmes (LIMOS), Ecole Nationale Supérieure des Mines de St Etienne (ENSM ST-ETIENNE)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne), Université Clermont Auvergne (UCA)-Université Clermont Auvergne (UCA), Rectorat de l'Académie de Clermont-Ferrand, Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Activité, Connaissance, Transmission, éducation (ACTé ), Université Clermont Auvergne (UCA), Maison pour la Science/Auvergne (MPSA), Laboratoire de Physique et Physiologie Intégratives de l’Arbre en environnement Fluctuant (PIAF), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), EFRAN-EP3C, and Ecole Nationale Supérieure des Mines de St Etienne-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national polytechnique Clermont Auvergne (INP Clermont Auvergne)

Subjects
Male, Computer and Information Sciences, Epidemiology, Cognitive Neuroscience, [SHS.EDU]Humanities and Social Sciences/Education, Science, Social Sciences, Academic Skills, Computer Applications, Education, Human Learning, Learning and Memory, Cognition, Sociology, Memory, Academic Performance, Medicine and Health Sciences, Humans, Learning, Psychology, Working Memory, Child, Pandemics, Schools, SARS-CoV-2, Cognitive Psychology, COVID-19, Biology and Life Sciences, Teachers, Professions, Memory, Short-Term, People and Places, [SCCO.PSYC]Cognitive science/Psychology, Cognitive Science, Medicine, Female, Population Groupings, [INFO.EIAH]Computer Science [cs]/Technology for Human Learning, Computer-Assisted Instruction, Research Article, Neuroscience
Abstract

International audience; The Covid-19 pandemic has led millions of students worldwide to intensify their use of digital education. This massive change is not reflected by the scant scientific research on the effectiveness of methods relying on digital learning compared to other innovative and more popular methods involving face-to-face interactions. Here, we tested the effectiveness of computer-assisted instruction (CAI) in Science and Technology compared to inquiry-based learning (IBL), another modern method which, however, requires students to interact with each other in the classroom. Our research also considered socio-cognitive factors–working memory (WM), socioeconomic status (SES), and academic self-concept (ASC)–known to predict academic performance but usually ignored in research on IBL and CAI. Five hundred and nine middle-school students, a fairly high sample size compared with relevant studies, received either IBL or CAI for a period varying from four to ten weeks prior to the Covid-19 events. After controlling for students’ prior knowledge and socio-cognitive factors, multilevel modelling showed that CAI was more effective than IBL. Although CAI-related benefits were stable across students’ SES and ASC, they were particularly pronounced for those with higher WM capacity. While indicating the need to adapt CAI for students with poorer WM, these findings further justify the use of CAI both in normal times (without excluding other methods) and during pandemic episodes.

Published
2021

5. Circulating 20S proteasome for assessing protein energy wasting syndrome in hemodialysis patients

Author

Marine Freist, Elodie Gentes, Carole Philipponnet, Mohamed Hadj Abdelkader, Bruno Pereira, Aurélien Piraud, Cyril Garrouste, Anne-Elisabeth Heng, Julien Aniort, Unité de Nutrition Humaine (UNH), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Centre Hospitalier Emile Roux [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Néphrologie - Hémodialyses [CHU Clermont-Ferrand], Pôle RHEUNNIRS [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand-CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Dept Clin Nutr, Unité de Biostatistiques [CHU Clermont-Ferrand], Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Unité de Biostatistiques, Direction de la Recherche Clinique (DRCI)

Subjects
Male, 0301 basic medicine, dialyse, [SDV]Life Sciences [q-bio], medicine.medical_treatment, 030232 urology & nephrology, Muscle Proteins, Biochemistry, protéasome, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Gastroenterology, 0302 clinical medicine, Medicine and Health Sciences, 2. Zero hunger, Multidisciplinary, Protein energy wasting, Muscle Analysis, Middle Aged, C-Reactive Proteins, Muscle atrophy, atrophie musculaire, 3. Good health, Hospitalization, Bioassays and Physiological Analysis, Nephrology, Creatinine, Medicine, Female, patient, Hemodialysis, medicine.symptom, Research Article, Proteasome Endopeptidase Complex, medicine.medical_specialty, Science, Nutritional Status, Circulating Proteasome, Research and Analysis Methods, Protein-Energy Malnutrition, 03 medical and health sciences, Signs and Symptoms, Renal Dialysis, Internal medicine, Medical Dialysis, medicine, Humans, Mortality, Survival rate, Nutrition, Aged, Wasting Syndrome, business.industry, Biology and Life Sciences, Proteins, Protein Complexes, Proteasomes, medicine.disease, perte d'énergie, Patient Outcome Assessment, 030104 developmental biology, Proteasome, Clinical Medicine, Atrophy, Complication, business, Biomarkers, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Kidney disease
Abstract

International audience; Protein energy wasting (PEW) including muscle atrophy is a common complication in chronic hemodialysis patients. The ubiquitin proteasome system (UPS) is the main proteolytic system causing muscle atrophy in chronic kidney disease and proteasome 20S is the catalytic component of the UPS. Circulating proteasome 20S (c20S proteasome) is present in the blood and its level is related to disease severity and prognosis in several disorders. We hypothesized that c20S proteasome could be related with muscle mass, other PEW criteria and their evolution in hemodialysis patients. Stable hemodialysis patients treated at our center for more than 3 months were followed over 2 years. C20S proteasome assay was performed at baseline. Biological and clinical data were collected, muscle mass was assessed by multi-frequency bio-impedancemetry, and nutritional scores were calculated at baseline, 1 year and 2 years. Hospitalizations and mortality data were collected over the 2 years. Forty-nine patients were included. At baseline, the c20S proteasome level was 0.40 [0.26-0.55] mu g/ml. Low muscle mass as defined by a lean tissue index (LTI) < 10th in accordance with the International Society of Renal Nutrition and Metabolism guidelines was observed in 36% and PEW in 62%. Increased c20S proteasome levels were related with LTI at baseline (R = 0.43, p = 0.004) and with its 2 year-variation (R = -0.56, p = 0.003). Two-year survival rate was not different between higher and lower c20S proteasome values (78.9 vs 78.4%, p = 0.98 log-rank test). C20S proteasome is not a good marker for assessing nutritional status in hemodialysis patients and predicting patient outcomes.

Published
2020

6. Development of an innovative methodology combining chemical fractionation and in vivo analysis to investigate the biological properties of cheese

Author

Anne Chauder, Julien Priam, Philippe Veisseire, Laurent Rios, Etienne Saunier, Stéphanie Bornes, Guillaume B Cardin, Pierre Chalard, Muriel Bonnet, Cyril Poupet, Isabelle Ripoche, Unité Mixte de Recherche sur le Fromage (UMRF), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut de Chimie de Clermont-Ferrand (ICCF), SIGMA Clermont (SIGMA Clermont)-Institut de Chimie du CNRS (INC)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Dômes Pharma, and Ministry of Education, Culture, Sports, Science and Technology, Japan (MEXT)Japan Society for the Promotion of ScienceVetAgro Sup United States Department of Health & Human ServicesNational Institutes of Health (NIH) - USAP40 OD010440

Subjects
0106 biological sciences, 0301 basic medicine, Biological test, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Nematoda, Organoleptic, Acetates, Chemical Fractionation, Water quality management, Biochemistry, 01 natural sciences, Cheese, Medicine and Health Sciences, Metabolites, Food science, Amphotericin, Fermentation in food processing, media_common, Extraction Techniques, 2. Zero hunger, Multidisciplinary, Antimicrobials, Organic Compounds, Goats, Chemical fractionation, Longevity, Eukaryota, Drugs, Animal Models, Lipids, Chemistry, Milk, Microbial biodiversity, Experimental Organism Systems, Caenorhabditis Elegans, Physical Sciences, Medicine, Cheeses, Hydrophobic and Hydrophilic Interactions, Research Article, media_common.quotation_subject, Science, Mycology, Complex Mixtures, Biology, Research and Analysis Methods, Microbiology, 03 medical and health sciences, Model Organisms, Cyclohexanes, Microbial Control, 010608 biotechnology, Biological property, Individual conditional expectation plots, Animals, Nutrition, Pharmacology, Methylene Chloride, Antifungals, Peri-alpine lakes, Ethanol, Organic Chemistry, Organisms, Chemical Compounds, Water, Biology and Life Sciences, In vivo analysis, Planktothrix rubescens, Invertebrates, Diet, Freeze Drying, Metabolism, 030104 developmental biology, Food, Alcohols, Solvents, Animal Studies, Caenorhabditis, Feasibility Studies, Forecast, Zoology, Food Analysis, Random forest
Abstract

With the ever-increasing human lifespan, age-related affections have become a public health issue. The health sector is looking for new bioactive compounds to respond to this demand. The unexplored microbial biodiversity and its metabolites represent a major source of innovative bioactive molecules with health potential. Fermented foods, such as raw-milk cheese, have already been investigated for their rich microbial environment, especially for their organoleptic qualities. But studies remain limited regarding their effects on health and few metabolites of microbial origin have been identified. An efficient methodology was developed in this study to investigate the biological effect of raw-milk cheese, combining a chemical fractionation, to isolate the most metabolites from the cheese matrix, and anin vivobiological test usingCaenorhabditis elegans.C.eleganswas brought into contact with cheese extracts, obtained by means of chemical fractionation, and with freeze-dried whole cheese by supplementing the nematode growth medium. A longevity assay was performed to evaluate the effects of the extracts on the worms. Our results demonstrate the feasibility of the method developed to bring the worms into contact of the cheese extracts. The evaluation of the effects of the extracts on the longevity was possible. Some extracts showed a beneficial effect as extract W70 for example, obtained with water, which increases the mean lifespan by 16% and extends the longevity by 73% (p< 0.0001).

Published
2020

7. Glutathione S Transferases Polymorphisms Are Independent Prognostic Factors in Lupus Nephritis Treated with Cyclophosphamide

Author

Alexandra Audemard-Verger, Nicolas Martin Silva, Céline Verstuyft, Nathalie Costedoat-Chalumeau, Aurélie Hummel, Véronique Le Guern, Karim Sacré, Olivier Meyer, Eric Daugas, Cécile Goujard, Audrey Sultan, Thierry Lobbedez, Lionel Galicier, Jacques Pourrat, Claire Le Hello, Michel Godin, Rémy Morello, Marc Lambert, Eric Hachulla, Philippe Vanhille, Guillaume Queffeulou, Jacky Potier, Jean-Jacques Dion, Pierre Bataille, Dominique Chauveau, Guillaume Moulis, Dominique Farge-Bancel, Pierre Duhaut, Bernadette Saint-Marcoux, Alban Deroux, Jennifer Manuzak, Camille Francès, Olivier Aumaitre, Holy Bezanahary, Laurent Becquemont, Boris Bienvenu, Université de Lausanne (UNIL), Département de Néphrologie et Transplantation d'organes, Faculté de Médecine [Rangueil], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse], Service de Néphrologie - Médecine Interne, CHU Amiens-Picardie-hôpital Sud, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Bases Moleculaires de l'Homeostasie Cutanee : Inflammation, Reparation et Cancer, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), Service de dermatologie [CHU d'Amiens-Picardie], CHU Amiens-Picardie, Mécanismes physiopathologiques et conséquences des calcifications vasculaires - UR UPJV 7517 (MP3CV), Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Service de dermatologie et allergologie [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Service de Médecine Interne [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Médecine interne A et polyclinique médicale [CHU Limoges], CHU Limoges, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Cochin [AP-HP], Unité de Biostatistique et de Recherche Clinique (UBRC), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Barrière et passage des médicaments, Université Paris-Sud - Paris 11 (UP11)-IFR141, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Référence des Maladies auto-immunes systémiques rares d'Ile-de-Frances [Hopital Cochin], CHU Necker - Enfants Malades [AP-HP], Service de médecine interne et centre de référence des maladies rares [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Université de Paris (UP), Laboratoire Génie électrique et électronique de Paris (GeePs), Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), UMR 1599, Centre National de la Recherche Scientifique (CNRS), Service de Médecine Interne et Immunologie clinique [AP-HP Hôpital Bicêtre], Hôpital Bicêtre, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Service de médecine interne [CHU Caen], Service de Néphrologie-Dialyse-Transplantation rénale [CHU Caen], Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Service de Néphrologie - Immunologie Clinique [Toulouse], CHU Toulouse [Toulouse]-PRES Université de Toulouse, Département de Médécine Vasculaire [CHU Caen], Nouvelles Cibles Pharmacologiques de la Protection Endothéliale et de l'Insuffisance Cardiaque (EnVI), CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Néphrologie [Rouen], Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Syndicat des eaux du Vivier, Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Lille, Hôpital Claude Huriez [Lille], Centre National de Référence des Maladies Auto-Immunes Systémiques Rares du Nord et Nord-Ouest de France (CeRAINO), Service de Néphrologie, Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Service de Néphrologie [CHPC - Site Louis Pasteur], Site Louis Pasteur [CHPC], CH Centre Hospitalier Public du Cotentin (CHPC)-CH Centre Hospitalier Public du Cotentin (CHPC), and CH Centre Hospitalier Public du Cotentin (CHPC)

Subjects
Male, Heredity, Physiology, [SDV]Life Sciences [q-bio], Lupus nephritis, lcsh:Medicine, Pharmacology, urologic and male genital diseases, Pathology and Laboratory Medicine, chemistry.chemical_compound, Mathematical and Statistical Techniques, 0302 clinical medicine, Drug Metabolism, Gene Frequency, Medicine and Health Sciences, lcsh:Science, Glutathione Transferase, Multidisciplinary, Proteinuria, Middle Aged, Lupus Nephritis, Genetic Mapping, Creatinine, 030220 oncology & carcinogenesis, Physical Sciences, Female, medicine.symptom, Glutathione S-Transferase pi, Statistics (Mathematics), Immunosuppressive Agents, Research Article, Glomerular Filtration Rate, medicine.drug, Adult, Drug-Related Side Effects and Adverse Reactions, Cyclophosphamide, Immunology, Variant Genotypes, Biology, Research and Analysis Methods, Polymorphism, Single Nucleotide, digestive system, Autoimmune Diseases, Young Adult, 03 medical and health sciences, Signs and Symptoms, Diagnostic Medicine, Genetics, medicine, Humans, Pharmacokinetics, Statistical Methods, Alleles, Genetic Association Studies, Retrospective Studies, 030203 arthritis & rheumatology, Renal Physiology, Evolutionary Biology, Population Biology, lcsh:R, Biology and Life Sciences, Glutathione, medicine.disease, Cytochrome P-450 CYP2C19, Cytochrome P-450 CYP2B6, chemistry, Genetic Loci, Multivariate Analysis, Genetic Polymorphism, lcsh:Q, Clinical Immunology, Clinical Medicine, Population Genetics, Mathematics, Drug metabolism
Abstract

International audience; Objective To investigate association between genetic polymorphisms of GST, CYP and renal outcome or occurrence of adverse drug reactions (ADRs) in lupus nephritis (LN) treated with cyclophosphamide (CYC). CYC, as a pro-drug, requires bioactivation through multiple hepatic cytochrome P450s and glutathione S transferases (GST). Methods We carried out a multicentric retrospective study including 70 patients with proliferative LN treated with CYC. Patients were genotyped for polymorphisms of the CYP2B6, CYP2C19, GSTP1, GSTM1 and GSTT1 genes. Complete remission (CR) was defined as proteinuria 105Val GSTP1 genotype were respectively 38%, 60% and 44%. In multivariate analysis, the Ile -> 105Val GSTP1 genotype was an independent factor of poor renal outcome (achievement of CR or PR) (OR = 5.01 95% CI [1.02-24.51]) and the sole factor that influenced occurrence of ADRs was the GSTM1 null genotype (OR = 3.34 95% CI [1.064-10.58]). No association between polymorphisms of cytochrome P450s gene and efficacy or ADRs was observed. Conclusion This study suggests that GST polymorphisms highly impact renal outcome and occurrence of ADRs related to CYC in LN patients.

Published
2016

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