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1
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Pérez-Gómez N, Fernández-Ortega MD, Elizari-Roncal M, Santos-Mazo E, la Maza-Pereg LD, Calvo S, Alcaraz R, Sanz-Solas A, Vinuesa R, Saiz-Rodríguez M. Identification of clinical and pharmacogenetic factors influencing metformin response in Type 2 diabetes mellitus. Pharmacogenomics 2023; 24:651-663. [PMID: 37610884 DOI: 10.2217/pgs-2023-0109] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/25/2023] Open
Abstract
Metformin, a hypoglycemic drug for Type 2 diabetes mellitus, shows variability in pharmacokinetics and response due to membrane transporters. This study followed 34 Type 2 diabetes mellitus patients on metformin treatment. Genetic variants in 11 metformin transport-related genes were analyzed, revealing associations. Specifically, SLC47A1 rs2289669 A/A and SLC22A4 rs1050152 T/T genotypes correlated with glycated hemoglobin values at 6 months. SLC47A1 rs2289669 G/A genotype influenced glucose levels at 6 months, while SLC29A4 rs3889348 A/A, SLC47A1 rs2289669 A/A, SLC22A4 rs1050152 C/T and SLC47A2 rs12943590 A/A genotypes were linked to glucose levels at 12 months. Additionally, ABCB1 rs2032582 C/A and ABCG2 rs2231137 C/T genotypes impacted cholesterol levels at 12 months. These findings shed light on metformin response determinants, offering insights for further research.
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Affiliation(s)
- Noelia Pérez-Gómez
- Department of Health Sciences, University of Burgos, Burgos, Spain
- Research Unit, Fundación Burgos por la Investigación de la Salud (FBIS), Hospital Universitario de Burgos, Burgos, Spain
| | | | - Miren Elizari-Roncal
- Health Center Jose Luis Santamaría, Burgos Primary Health Care Management, Burgos, Spain
| | | | | | - Sara Calvo
- Research Unit, Fundación Burgos por la Investigación de la Salud (FBIS), Hospital Universitario de Burgos, Burgos, Spain
| | - Raquel Alcaraz
- Research Unit, Fundación Burgos por la Investigación de la Salud (FBIS), Hospital Universitario de Burgos, Burgos, Spain
| | - Antonio Sanz-Solas
- Research Unit, Fundación Burgos por la Investigación de la Salud (FBIS), Hospital Universitario de Burgos, Burgos, Spain
| | - Raquel Vinuesa
- Research Unit, Fundación Burgos por la Investigación de la Salud (FBIS), Hospital Universitario de Burgos, Burgos, Spain
| | - Miriam Saiz-Rodríguez
- Department of Health Sciences, University of Burgos, Burgos, Spain
- Research Unit, Fundación Burgos por la Investigación de la Salud (FBIS), Hospital Universitario de Burgos, Burgos, Spain
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Wu J, Wang X, Chen H, Yang R, Yu H, Wu Y, Hu Y. Type 2 Diabetes Risk and Lipid Metabolism Related to the Pleiotropic Effects of an ABCB1 Variant: A Chinese Family-Based Cohort Study. Metabolites 2022; 12:metabo12090875. [PMID: 36144279 PMCID: PMC9502507 DOI: 10.3390/metabo12090875] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2022] [Revised: 09/07/2022] [Accepted: 09/08/2022] [Indexed: 11/23/2022] Open
Abstract
The single nucleotide polymorphism (SNP) rs4148727 in ABCB1 (encoding p-glycoprotein) is associated with lipid levels; however, its association with type 2 diabetes (T2DM) and its the genetic correlation with lipid profiles and T2DM are unclear. We included 2300 participants from 593 families. A generalized estimating equations (GEE) model and Cox regression models were used to estimate the SNP’s effects on T2DM and lipid profiles. The participation of the SNP in T2DM pathogenesis through lipid-associated pathways was tested using mediation analysis. The G allele of the SNP was related to a 32% (6–64%, p = 0.015) increase in T2DM risk. It was also associated with a 10% (1–20%, p = 0.029), 17% (3–32%, p = 0.015), and 4% (1–7%, p = 0.015) increment in total cholesterol (TC), triglyceride (TG), and apolipoprotein A (Apo-A) concentrations, respectively. According to the mediation analysis, only TG (6.9%) and Apo-B (4.0%) had slight but significant mediation effects on the total impact of the SNP on T2DM. The pleiotropic effects of the ABCB1 variant on T2DM and lipids likely act via different pathways. The biological mechanisms should be verified in a future study.
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Affiliation(s)
- Junhui Wu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China
- School of Nursing, Peking University, No. 38 Xueyuan Road, Beijing 100191, China
| | - Xiaowen Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China
| | - Hongbo Chen
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China
- School of Nursing, Peking University, No. 38 Xueyuan Road, Beijing 100191, China
| | - Ruotong Yang
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China
| | - Huan Yu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China
| | - Yiqun Wu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China
- Correspondence: (Y.W.); (Y.H.); Tel./Fax: +86-10-82801189 (Y.H.)
| | - Yonghua Hu
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University, Beijing 100191, China
- Medical Informatics Center, Peking University, Beijing 100191, China
- Correspondence: (Y.W.); (Y.H.); Tel./Fax: +86-10-82801189 (Y.H.)
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Iannuzzo G, Cuomo G, Di Lorenzo A, Tripaldella M, Mallardo V, Iaccarino Idelson P, Sagnelli C, Sica A, Creta M, Baltar J, Crocetto F, Bresciani A, Gentile M, Calogero A, Giallauria F. Dyslipidemia in Transplant Patients: Which Therapy? J Clin Med 2022; 11:4080. [PMID: 35887846 PMCID: PMC9318180 DOI: 10.3390/jcm11144080] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 07/11/2022] [Accepted: 07/11/2022] [Indexed: 12/17/2022] Open
Abstract
Cardiovascular disease is the most important cause of death worldwide in recent years; an increasing trend is also shown in organ transplant patients subjected to immunosuppressive therapies, in which cardiovascular diseases represent one of the most frequent causes of long-term mortality. This is also linked to immunosuppressant-induced dyslipidemia, which occurs in 27 to 71% of organ transplant recipients. The aim of this review is to clarify the pathophysiological mechanisms underlying dyslipidemia in patients treated with immunosuppressants to identify immunosuppressive therapies which do not cause dyslipidemia or therapeutic pathways effective in reducing hypercholesterolemia, hypertriglyceridemia, or both, without further adverse events.
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Affiliation(s)
- Gabriella Iannuzzo
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.I.); (M.T.); (V.M.); (P.I.I.); (M.G.)
| | - Gianluigi Cuomo
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.C.); (A.D.L.); (F.G.)
| | - Anna Di Lorenzo
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.C.); (A.D.L.); (F.G.)
| | - Maria Tripaldella
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.I.); (M.T.); (V.M.); (P.I.I.); (M.G.)
| | - Vania Mallardo
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.I.); (M.T.); (V.M.); (P.I.I.); (M.G.)
| | - Paola Iaccarino Idelson
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.I.); (M.T.); (V.M.); (P.I.I.); (M.G.)
| | - Caterina Sagnelli
- Department of Mental Health and Public Medicine, University of Campania “Luigi Vanvitelli”, Via S. Pansini 5, 80131 Naples, Italy;
| | - Antonello Sica
- Department of Precision Medicine University of Campania “Luigi Vanvitelli”, Naples, Via S. Pansini 5, 80131 Naples, Italy;
| | - Massimiliano Creta
- Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, Naples, Via S. Pansini 5, 80131 Naples, Italy; (M.C.); (F.C.)
| | - Javier Baltar
- Servicio de Cirugía General, Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), 15706 Santiago de Compostela, Spain;
| | - Felice Crocetto
- Department of Neurosciences, Reproductive Sciences and Odontostomatology, University of Naples Federico II, Naples, Via S. Pansini 5, 80131 Naples, Italy; (M.C.); (F.C.)
| | - Alessandro Bresciani
- Department of Medicine and Medical Specialties, A. Cardarelli Hospital, 80131 Naples, Italy;
| | - Marco Gentile
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.I.); (M.T.); (V.M.); (P.I.I.); (M.G.)
| | - Armando Calogero
- Servicio de Cirugía General, Xerencia de Xestión Integrada de Santiago (XXIS/SERGAS), 15706 Santiago de Compostela, Spain;
| | - Francesco Giallauria
- Department of Translational Medical Sciences, University of Naples Federico II, Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.C.); (A.D.L.); (F.G.)
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Cuomo G, Cioffi G, Di Lorenzo A, Iannone FP, Cudemo G, Iannicelli AM, Pacileo M, D’Andrea A, Vigorito C, Iannuzzo G, Giallauria F. Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors Use for Atherogenic Dyslipidemia in Solid Organ Transplant Patients. J Clin Med 2022; 11:3247. [PMID: 35683632 PMCID: PMC9180971 DOI: 10.3390/jcm11113247] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Revised: 06/03/2022] [Accepted: 06/04/2022] [Indexed: 01/27/2023] Open
Abstract
Dyslipidemia is a widespread risk factor in solid organ transplant patients, due to many reasons, such as the use of immunosuppressive drugs, with a consequent increase in cardiovascular diseases in this population. PCSK9 is an enzyme mainly known for its role in altering LDL levels, consequently increasing cardiovascular risk. Monoclonal antibody PCSK9 inhibitors demonstrated remarkable efficacy in the general population in reducing LDL cholesterol levels and preventing cardiovascular disease. In transplant patients, these drugs are still poorly used, despite having comparable efficacy to the general population and giving fewer drug interactions with immunosuppressants. Furthermore, there is enough evidence that PCSK9 also plays a role in other pathways, such as inflammation, which is particularly dangerous for graft survival. In this review, the current evidence on the function of PCSK9 and the use of its inhibitors will be discussed, particularly in transplant patients, in which they may provide additional benefits.
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Affiliation(s)
- Gianluigi Cuomo
- Department of Translational Medical Sciences, “Federico II” University of Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.C.); (G.C.); (A.D.L.); (G.C.); (A.M.I.); (C.V.)
| | - Giuseppe Cioffi
- Department of Translational Medical Sciences, “Federico II” University of Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.C.); (G.C.); (A.D.L.); (G.C.); (A.M.I.); (C.V.)
| | - Anna Di Lorenzo
- Department of Translational Medical Sciences, “Federico II” University of Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.C.); (G.C.); (A.D.L.); (G.C.); (A.M.I.); (C.V.)
| | - Francesca Paola Iannone
- Department of Clinical Medicine and Surgery, “Federico II” University of Naples, Via S. Pansini 5, 80131 Naples, Italy; (F.P.I.); (G.I.)
| | - Giuseppe Cudemo
- Department of Translational Medical Sciences, “Federico II” University of Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.C.); (G.C.); (A.D.L.); (G.C.); (A.M.I.); (C.V.)
| | - Anna Maria Iannicelli
- Department of Translational Medical Sciences, “Federico II” University of Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.C.); (G.C.); (A.D.L.); (G.C.); (A.M.I.); (C.V.)
| | - Mario Pacileo
- Unit of Cardiology and Intensive Care, Umberto I Hospital, 84014 Nocera Inferiore, Italy; (M.P.); (A.D.)
| | - Antonello D’Andrea
- Unit of Cardiology and Intensive Care, Umberto I Hospital, 84014 Nocera Inferiore, Italy; (M.P.); (A.D.)
| | - Carlo Vigorito
- Department of Translational Medical Sciences, “Federico II” University of Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.C.); (G.C.); (A.D.L.); (G.C.); (A.M.I.); (C.V.)
| | - Gabriella Iannuzzo
- Department of Clinical Medicine and Surgery, “Federico II” University of Naples, Via S. Pansini 5, 80131 Naples, Italy; (F.P.I.); (G.I.)
| | - Francesco Giallauria
- Department of Translational Medical Sciences, “Federico II” University of Naples, Via S. Pansini 5, 80131 Naples, Italy; (G.C.); (G.C.); (A.D.L.); (G.C.); (A.M.I.); (C.V.)
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Weight Gain After Heart Transplantation in Adults: Systematic Review and Meta-Analysis. ASAIO J 2021; 68:1107-1116. [PMID: 34560719 DOI: 10.1097/mat.0000000000001566] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022] Open
Abstract
Gain in weight is common after heart transplantation but the magnitude of usual weight gain and whether this varies by country is unknown. We systematically reviewed all relevant studies to quantify weight change among heart transplant recipients (HTRs) in the years after transplantation and assess variation with geographic location. We searched PubMed, Cumulative Index to Nursing and Allied Health Literature, and Excerpta Medica Database databases to September 2020. Eligible studies reported adult HTRs' mean/median weight and/or body mass index (BMI) up to time of transplantation (baseline) and posttransplantation in any language. Weighted mean differences (WMDs) (95% confidence intervals [CIs]) of weight/BMI from baseline to posttransplantation were estimated using a random-effects model. Ten studies met the inclusion criteria. Pooled analysis showed weight gain of 7.1 kg (95% CI, 4.4-9.8 kg) in HTRs 12 months posttransplant, with corresponding BMI increase of 1.69 kg/m2 (95% CI, 0.83-2.55 kg/m2). Greatest weight gain at 12 months posttransplant occurred in US HTRs (WMD weight 10.42 kg, BMI 3.25 kg/m2) and least, in European HTRs (WMD weight 3.10 kg, BMI 0.78 kg/m2). In conclusion, HTRs gain substantial weight in the years after transplantation, but varying widely by geographic location.
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Boekstegers F, Marcelain K, Barahona Ponce C, Baez Benavides PF, Müller B, de Toro G, Retamales J, Barajas O, Ahumada M, Morales E, Rojas A, Sanhueza V, Loader D, Rivera MT, Gutiérrez L, Bernal G, Ortega A, Montalvo D, Portiño S, Bertrán ME, Gabler F, Spencer L, Olloquequi J, González Silos R, Fischer C, Scherer D, Jenab M, Aleksandrova K, Katzke V, Weiderpass E, Moradi T, Fischer K, Bossers W, Brenner H, Hveem K, Eklund N, Völker U, Waldenberger M, Fuentes Guajardo M, Gonzalez-Jose R, Bedoya G, Bortolini MC, Canizales S, Gallo C, Ruiz Linares A, Rothhammer F, Lorenzo Bermejo J. ABCB1/4 gallbladder cancer risk variants identified in India also show strong effects in Chileans. Cancer Epidemiol 2020; 65:101643. [PMID: 32058310 DOI: 10.1016/j.canep.2019.101643] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Revised: 11/08/2019] [Accepted: 11/15/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND The first large-scale genome-wide association study of gallbladder cancer (GBC) recently identified and validated three susceptibility variants in the ABCB1 and ABCB4 genes for individuals of Indian descent. We investigated whether these variants were also associated with GBC risk in Chileans, who show the highest incidence of GBC worldwide, and in Europeans with a low GBC incidence. METHODS This population-based study analysed genotype data from retrospective Chilean case-control (255 cases, 2042 controls) and prospective European cohort (108 cases, 181 controls) samples consistently with the original publication. RESULTS Our results confirmed the reported associations for Chileans with similar risk effects. Particularly strong associations (per-allele odds ratios close to 2) were observed for Chileans with high Native American (=Mapuche) ancestry. No associations were noticed for Europeans, but the statistical power was low. CONCLUSION Taking full advantage of genetic and ethnic differences in GBC risk may improve the efficiency of current prevention programs.
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Affiliation(s)
- Felix Boekstegers
- Statistical Genetics Group, Institute of Medical Biometry and Informatics, University of Heidelberg, Germany
| | - Katherine Marcelain
- Department of Basic and Clinical Oncology, Medical Faculty, University of Chile, Chile
| | - Carol Barahona Ponce
- Statistical Genetics Group, Institute of Medical Biometry and Informatics, University of Heidelberg, Germany; Department of Basic and Clinical Oncology, Medical Faculty, University of Chile, Chile
| | | | - Bettina Müller
- Servicio de Oncología Médica, Instituto Nacional del Cáncer, Santiago, Chile
| | - Gonzalo de Toro
- Servicio de Anatomía Patológica, Hospital de Puerto Montt, Puerto Montt, Chile
| | - Javier Retamales
- Servicio de Oncología Médica, Instituto Nacional del Cáncer, Santiago, Chile
| | - Olga Barajas
- Department of Basic and Clinical Oncology, Medical Faculty, University of Chile, Chile; Oncology, Hospital Clínico Universidad de Chile, Santiago, Chile
| | - Monica Ahumada
- Department of Basic and Clinical Oncology, Medical Faculty, University of Chile, Chile; Oncology, Hospital Clínico Universidad de Chile, Santiago, Chile
| | - Erik Morales
- Servicio de Anatomía Patológica, Hospital Regional, Talca, Chile
| | - Armando Rojas
- Biomedical Research Labs, Medicine Faculty, Catholic University of Maule, Talca, Chile
| | - Verónica Sanhueza
- Servicio de Anatomía Patológica, Hospital Padre Hurtado, Santiago, Chile
| | - Denisse Loader
- Servicio de Anatomía Patológica, Hospital Padre Hurtado, Santiago, Chile
| | | | - Lorena Gutiérrez
- Servicio de Anatomía Patológica, Hospital San Juan de Dios, Santiago, Chile
| | - Giuliano Bernal
- Laboratory of Molecular and Cellular Biology of Cancer (CancerLab), Department of Biomedical Sciences, Faculty of Medicine, Universidad Católica del Norte, Coquimbo, Chile
| | - Alejandro Ortega
- Servicio de Anatomía Patológica, Hospital Regional, Arica, Chile
| | | | - Sergio Portiño
- Oncology, Hospital Clínico Universidad de Chile, Santiago, Chile
| | | | - Fernando Gabler
- Servicio de Anatomía Patológica, Hospital San Borja Arriarán, Santiago, Chile
| | - Loreto Spencer
- Servicio de Anatomía Patológica, Hospital Regional Guillermo Grant Benavente, Concepción, Chile
| | - Jordi Olloquequi
- Laboratory of Cellular and Molecular Pathology, Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de Chile, Talca, Chile
| | - Rosa González Silos
- Statistical Genetics Group, Institute of Medical Biometry and Informatics, University of Heidelberg, Germany
| | | | - Dominique Scherer
- Statistical Genetics Group, Institute of Medical Biometry and Informatics, University of Heidelberg, Germany
| | - Mazda Jenab
- International Agency for Research on Cancer (IARC), World Health Organization, Lyon, France
| | - Krasimira Aleksandrova
- Nutrition, Immunity and Metabolism Senior Scientist Group, Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Nuthetal, Germany; University of Potsdam, Institute of Nutritional Science, Potsdam, Germany
| | - Verena Katzke
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Elisabete Weiderpass
- International Agency for Research on Cancer (IARC), World Health Organization, Lyon, France
| | - Tahereh Moradi
- Division of Epidemiology, Department of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Krista Fischer
- Estonian Genome Centre, Institute of Genomics, University of Tartu, Estonia
| | | | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), German Cancer Consortium (DKTK), Heidelberg, Germany
| | - Kristian Hveem
- The Nord-Trøndelag Health (HUNT) Research Centre, Norwegian University of Science and Technology (NTNU), Trondheim, K.G. Jebsen Centre for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Norway
| | - Niina Eklund
- Genomics and biobank, National Institute for Health and Welfare (THL), Helsinki, Finland
| | - Uwe Völker
- Interfakultäres Institut für Genetik und Funktionelle Genomforschung, Universitätsmedizin Greifswald, Germany
| | - Melanie Waldenberger
- Research Unit of Molecular Epidemiology and Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
| | | | - Rolando Gonzalez-Jose
- Instituto Patagónico de Ciencias Sociales y Humanas, Centro Nacional Patagónico, CONICET, Puerto Madryn, Argentina
| | - Gabriel Bedoya
- Facultad de Ciencias Exactas y Naturales, Universidad de Antioquia, Medellín, Colombia
| | - Maria C Bortolini
- Instituto de Biociências, Universidad Federal do Rio Grande do Sul, Puerto Alegre, Brazil
| | - Samuel Canizales
- Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, Mexico
| | - Carla Gallo
- Unidad de Neurobiología Molecular y Genética, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru
| | - Andres Ruiz Linares
- Ministry of Education Key Laboratory of Contemporary Anthropology and Collaborative Innovation Center of Genetics and Development, School of Life Sciences and Human Phenome Institute, Fudan University, Shanghai 200433, China; Aix-Marseille Univ, CNRS, EFS, ADES, Marseille 13007, France
| | | | - Justo Lorenzo Bermejo
- Statistical Genetics Group, Institute of Medical Biometry and Informatics, University of Heidelberg, Germany.
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Premstaller M, Perren M, Koçack K, Arranto C, Favre G, Lohri A, Gerull S, Passweg JR, Halter JP, Leuppi-Taegtmeyer AB. Dyslipidemia and lipid-lowering treatment in a hematopoietic stem cell transplant cohort: 25 years of follow-up data. J Clin Lipidol 2017; 12:464-480.e3. [PMID: 29310991 DOI: 10.1016/j.jacl.2017.11.008] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2017] [Revised: 11/22/2017] [Accepted: 11/27/2017] [Indexed: 10/18/2022]
Abstract
BACKGROUND Dyslipidemia is common after hematopoietic stem cell transplantation (HSCT). Few data regarding the time course of lipid profiles after HSCT, the effect of multiple transplantations, and efficacy and safety of lipid-lowering treatments are available. OBJECTIVE The objective of the study was to determine the prevalence and treatment of dyslipidemia over a 25-year period in a large, single-center cohort. METHODS One thousand one hundred ninety-six adult patients (≥16 years) who underwent HSCT during 1973 to 2013 and who survived ≥100 days were studied retrospectively. RESULTS The prevalence of dyslipidemia before transplantation was 36% and 28% in the autologous and allogeneic groups, respectively (P < .001). Three months after HSCT, the prevalence rose to 62% and 74% (P < .001), and at 25 years, it was 67% and 89%. Lipid profiles were similar after first and subsequent transplants. Baseline dyslipidemia (odds ratio [OR] = 2.72), allogeneic transplant (OR = 2.44), and age ≥ 35 years (OR = 2.33) were independent risk factors for dyslipidemia at 1 year. Lipid-lowering treatment was given to 223 (19%) patients, primarily in the form of statins (86%) and was associated with a decrease in total cholesterol from 246 to 192 mg/dL (P < .01) and from 244 to 195 mg/dL (P < .001) in the autologous and allogeneic groups, respectively. There were 10 cases (4%) of muscle symptoms prompting cessation of lipid-lowering therapy, including 1 case of rhabdomyolysis. The OR for dyslipidemia among patients who suffered a cardiovascular event (conditional logistic regression) was 3.5 (95% confidence interval = 1.6-7.7, P = .002). CONCLUSION This study confirms that dyslipidemia is a common and long-lasting phenomenon among both allogeneic and autologous HSCT patients. Statins are effective, generally well-tolerated and should be highly recommended for the management of post-HSCT dyslipidemia.
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Affiliation(s)
- Melanie Premstaller
- Medical University Clinic, Cantonal Hospital Baselland, Liestal and University of Basel, Basel, Switzerland
| | - Melanie Perren
- Department of Clinical Pharmacology and Toxicology, University Hospital Basel and University of Basel, Basel, Switzerland
| | - Kuebra Koçack
- Department of Clinical Pharmacology and Toxicology, University Hospital Basel and University of Basel, Basel, Switzerland
| | - Christian Arranto
- Department of Hematology, University Hospital Basel and University of Basel, Basel, Switzerland
| | - Geneviève Favre
- Medical University Clinic, Cantonal Hospital Baselland, Liestal and University of Basel, Basel, Switzerland
| | - Andreas Lohri
- Medical University Clinic, Cantonal Hospital Baselland, Liestal and University of Basel, Basel, Switzerland
| | - Sabine Gerull
- Department of Hematology, University Hospital Basel and University of Basel, Basel, Switzerland
| | - Jakob R Passweg
- Department of Hematology, University Hospital Basel and University of Basel, Basel, Switzerland
| | - Jörg P Halter
- Department of Hematology, University Hospital Basel and University of Basel, Basel, Switzerland
| | - Anne B Leuppi-Taegtmeyer
- Department of Clinical Pharmacology and Toxicology, University Hospital Basel and University of Basel, Basel, Switzerland.
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8
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The ABCB1 2677G>T/A polymorphism is associated with baseline blood HDL-cholesterol levels in newly diagnosed hyperlipidemic patients. Hellenic J Cardiol 2017; 59:122-126. [PMID: 28189737 DOI: 10.1016/j.hjc.2017.01.023] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2015] [Accepted: 09/06/2016] [Indexed: 11/22/2022] Open
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Grezzana GB, Vieira JLDC, Portal VL. Single-nucleotide polymorphisms: a perspective of cardiovascular prevention. Rev Assoc Med Bras (1992) 2016; 61:458-68. [PMID: 26603010 DOI: 10.1590/1806-9282.61.05.458] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2014] [Accepted: 10/21/2014] [Indexed: 11/22/2022] Open
Abstract
INTRODUCTION several studies have evaluated the utilization of lipid biomarkers in an attempt to correlate them with clinical cardiovascular events. Nevertheless, the investigation of clinical conditions under specific plasmatic levels of lipoproteins for long periods presents limitations due to inherent difficulties that are related to the follow-up of individuals throughout their lives. Better understanding of the clinical response and occasional resistance to the action of hypolipidemic drugs in several clinic scenarios is also necessary. OBJECTIVES to determine the role of evaluation of single-nucleotide polymorphisms (SNPs) related to the metabolism of lipids, and its implications in different clinical scenarios. METHODS a search of the literature in English and Spanish languages was performed in Medline, Lilacs via Bireme, IBECS via Bireme, and Cochrane databases. The expected results included information regarding plasmatic lipid profile and SNPs, cardiovascular clinical outcomes and polymorphisms related to the effectiveness of statins in the treatment of hypercholesterolemia. RESULTS in order to perform this analysis, 19 studies were included from a total of 89 identified citations. The evaluation of the results suggests that low plasmatic levels of LDL-c are associated with a reduction in the risk of heart attacks, although this was not observed for the rise of plasmatic levels of HDL-c. CONCLUSION polymorphisms in different populations and clinical perspectives may bring important contributions for a better understanding and adequacy of plasmatic lipoproteins aiming at reducing cardiovascular risk.
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Affiliation(s)
- Guilherme Brasil Grezzana
- Instituto de Cardiologia do Rio Grande do Sul, Fundação Universitária de Cardiologia, Porto Alegre, RS, Brazil
| | - José Luiz da Costa Vieira
- Medical Residency Outpatient Clinic, IC, Fundação Universitária de Cardiologia, Porto Alegre, RS, Brazil
| | - Vera Lúcia Portal
- Graduate Program in Health Sciences, IC, Fundação Universitária de Cardiologia, Porto Alegre, RS, Brazil
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Gbandi E, Goulas A, Sevastianos V, Hadziyannis S, Panderi A, Koskinas J, Papatheodoridis G, Vasiliadis T, Agapakis D, Protopapas A, Ioannidou P, Zacharakis G, Sinakos E, Koutsounas S, Germanidis G. Common ABCB1 polymorphisms in Greek patients with chronic hepatitis C infection: A comparison with hyperlipidemic patients and the general population. Pharmacol Rep 2016; 68:476-482. [PMID: 26922556 DOI: 10.1016/j.pharep.2015.10.009] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2015] [Revised: 10/23/2015] [Accepted: 10/23/2015] [Indexed: 01/18/2023]
Abstract
BACKGROUND Hepatitis C virus infectivity and replication efficiency appears to be dependent on the lipid content and organization of the plasma membrane of the host cell, as well as of the intracellular membranous web. As there is increasing awareness of a role played by the efflux pump ABCB1 (p-glycoprotein, P-gp) in lipid homeostasis, its function could be a determinant of chronic HCV infection. The aim of the present study was to examine and compare the distribution of common ABCB1 genotypes in patients with chronic HCV infection (n=168), hyperlipidemic patients (n=168) and a control group (n=173), all from Greece. METHODS Participants were genotyped for the ABCB12677G>T/A and 3435C>T polymorphisms with previously reported PCR-RFLP methods. Genotype and allele frequency distributions were compared between the three groups with the χ(2) test of independence. RESULTS The ABCB1 2677GG (ancestral) genotypes were significantly over-represented in patients with chronic hepatitis C compared to controls (39.3% vs. 26.6%, p=0.015 according to the dominant model). A similar result was obtained when hyperlipidemic patients were compared to controls (45.2% vs. 26.6%, p<0.001 according to the dominant model). Comparison of ABCB1 3435C>T genotype and allele distributions provided similar but not as significant differences. Genotype and allele distributions for both ABCB12677G>T/A and 3435C>T were very similar between HCV patients and hyperlipidemic patients. CONCLUSION Our findings imply an influence of ABCB1 polymorphisms on HCV infectivity, possibly through an effect on lipid homeostasis.
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Affiliation(s)
- Emma Gbandi
- 1st Department of Pharmacology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Antonis Goulas
- 1st Department of Pharmacology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece.
| | | | | | - Athanasia Panderi
- 1st Department of Pharmacology, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - John Koskinas
- 2nd Academic Department of Internal Medicine, Hippokration Hospital of Athens, Athens, Greece
| | - George Papatheodoridis
- Department of Gastroenterology, Athens University Medical School, Laikon General Hospital of Athens, Athens, Greece
| | - Themistoklis Vasiliadis
- 3rd Department of Internal Medicine, Papageorgiou Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Dimitrios Agapakis
- 1st Propedeutic Department of Internal Medicine, AHEPA Hospital, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Andreas Protopapas
- 1st Propedeutic Department of Internal Medicine, AHEPA Hospital, Faculty of Medicine, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Panagiota Ioannidou
- Department of Gastroenterology, Athens University Medical School, Laikon General Hospital of Athens, Athens, Greece
| | - George Zacharakis
- 2nd Department of Gastroenterology, Evangelismos General Hospital of Athens, Athens, Greece
| | - Emmanuil Sinakos
- 4th Department of Internal Medicine, Aristotle University of Thessaloniki Medical School, Hippokration General Hospital, Thessaloniki, Greece
| | | | - Georgios Germanidis
- 1st Department of Internal Medicine, AHEPA Hospital, Aristotle University of Thessaloniki, School of Medicine, Thessaloniki, Greece
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Agarwal A, Prasad GVR. Post-transplant dyslipidemia: Mechanisms, diagnosis and management. World J Transplant 2016; 6:125-134. [PMID: 27011910 PMCID: PMC4801788 DOI: 10.5500/wjt.v6.i1.125] [Citation(s) in RCA: 77] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2015] [Revised: 11/26/2015] [Accepted: 02/17/2016] [Indexed: 02/05/2023] Open
Abstract
Post-transplant dyslipidemia is highly prevalent and presents unique management challenges to the clinician. The two major outcomes to consider with post-transplant therapies for dyslipidemia are preserving or improving allograft function, and reducing cardiovascular risk. Although there are other cardiovascular risk factors such as graft dysfunction, hypertension, and diabetes, attention to dyslipidemia is warranted because interventions for dyslipidemia have an impact on reducing cardiac events in clinical trials specific to the transplant population. Dyslipidemia is not synonymous with hyperlipidemia. Numerous mechanisms exist for the occurrence of post-transplant dyslipidemia, including those mediated by immunosuppressive drug therapy. Statin therapy has received the most attention in all solid organ transplant recipient populations, although the effect of proper dietary advice and adjuvant pharmacological and non-pharmacological agents should not be dismissed. At all stages of treatment appropriate monitoring strategies for side effects should be implemented so that the benefits from these therapies can be achieved. Clinicians have a choice when there is a conflict between various transplant society and lipid society guidelines for therapy and targets.
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Venuto RC, Meaney CJ, Chang S, Leca N, Consiglio JD, Wilding GE, Brazeau D, Gundroo A, Nainani N, Morse SE, Cooper LM, Tornatore KM. Association of Extrarenal Adverse Effects of Posttransplant Immunosuppression With Sex and ABCB1 Haplotypes. Medicine (Baltimore) 2015; 94:e1315. [PMID: 26376376 PMCID: PMC4635790 DOI: 10.1097/md.0000000000001315] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2015] [Revised: 06/25/2015] [Accepted: 07/13/2015] [Indexed: 01/28/2023] Open
Abstract
Extrarenal adverse effects (AEs) associated with calcineurin inhibitor (CNI) and mycophenolic acid (MPA) occur frequently but are unpredictable posttransplant complications. AEs may result from intracellular CNI accumulation and low activity of P-glycoprotein, encoded by the ABCB1 gene. Since ABCB1 single nucleotide polymorphisms (SNPs) and sex influence P-glycoprotein, we investigated haplotypes and extrarenal AEs. A prospective, cross-sectional study evaluated 149 patients receiving tacrolimus and enteric coated mycophenolate sodium or cyclosporine and mycophenolate mofetil. Immunosuppressive AE assessment determined individual and composite gastrointestinal, neurologic, aesthetic, and cumulative AEs. Lipids were quantitated after 12-hour fast. ABCB1 SNPs: c.1236C>T (rs1128503), c.2677G>T/A (rs2032582), and c.3435C>T (rs1045642) were determined with haplotype associations computed using the THESIAS program, and evaluated by immunosuppression, sex and race using multivariate general linear models. Tacrolimus patients exhibited more frequent and higher gastrointestinal AE scores compared with cyclosporine with association to CTT (P = 0.018) and sex (P = 0.01). Aesthetic AE score was 3 times greater for cyclosporine with TTC haplotype (P = 0.005). Females had higher gastrointestinal (P = 0.022), aesthetic (P < 0.001), neurologic (P = 0.022), and cumulative AE ratios (P < 0.001). Total cholesterol (TCHOL), low-density lipoproteins (LDL), and triglycerides were higher with cyclosporine. The TTC haplotype had higher TCHOL (P < 0.001) and LDL (P = 0.005). Higher triglyceride (P = 0.034) and lower high-density lipoproteins (P = 0.057) were associated with TTT with sex-adjusted analysis. ABCB1 haplotypes and sex were associated with extrarenal AEs. Using haplotypes, certain female patients manifested more AEs regardless of CNI. Haplotype testing may identify patients with greater susceptibility to AEs and facilitate CNI individualization.
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Affiliation(s)
- Rocco C Venuto
- From the Nephrology Division; Medicine, School of Medicine and Biomedical Sciences (RCV, SC, NL, AG, NN, KMT); Erie County Medical Center, Buffalo, New York (RCV, AG, KMT); Immunosuppressive Pharmacology Research Program, Translational Pharmacology Research Core, NYS Center of Excellence in Bioinformatics and Life Sciences (CJM, SEM, LMC, KMT); Pharmacy, School of Pharmacy and Pharmaceutical Sciences (CJM, SEM, KMT); Biostatistics, School of Public Health and Health Professions, University at Buffalo, Buffalo, New York (JDC, GEW); and Department of Pharmaceutical Sciences, College of Pharmacy, University of New England, Portland, Maine (DB)
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Li Q, Hong J, Wu J, Huang ZX, Li QJ, Yin RX, Lin QZ, Wang F. The role of common variants of ABCB1 and CYP7A1 genes in serum lipid levels and lipid-lowering efficacy of statin treatment: a meta-analysis. J Clin Lipidol 2014; 8:618-629. [PMID: 25499945 DOI: 10.1016/j.jacl.2014.07.010] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2014] [Revised: 07/23/2014] [Accepted: 07/30/2014] [Indexed: 01/17/2023]
Abstract
BACKGROUND The relation between the ABCB1 and CYP7A1 genes and serum lipid levels and lipid-lowering efficacy of statin treatment is inconsistent. OBJECTIVE The purpose of this meta-analysis was to explore the associations between the ABCB1 and CYP7A1 genes and serum lipid levels and lipid-lowering efficacy of statin treatment. METHODS MEDLINE, EMBASE, and the Cochrane Library databases were searched systematically for studies of associations between relevant single nucleotide polymorphisms C3435 T (ABCB1), G2677 A/T (ABCB1), and A-204C (CYP7A1) and serum lipid levels or statin treatment. Associations were assessed in pooled data by calculating mean difference with 95% confidence intervals. RESULTS Seventeen studies with 4890 patients were included in this meta-analysis. The "AA" group at A-204C (CYP7A1) had lower serum total cholesterol (TC) levels than "AC + CC" group. The "AA" group at A-204C (CYP7A1) had greater reduction in low-density lipoprotein cholesterol (LDL-C) with statin treatment than "AC + CC" group. The "GG" group at G2677 A/T (ABCB1) had less reduction in TC and LDL-C with statin treatment than "non-GG" group. CONCLUSIONS The A-204C (CYP7A1) polymorphism was associated with the level of TC and the lipid-lowering efficacy of statin treatment in the level of LDL-C. The G2677 A/T (ABCB1) polymorphism was associated with the lipid-lowering efficacy of statin treatment in the levels of LDL-C and TC.
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Affiliation(s)
- Qing Li
- Department of Internal Medicine, Affiliated Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Jiang Hong
- Department of Internal Medicine, Affiliated Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China
| | - Jian Wu
- Department of Cardiology, Institute of Cardiovascular Diseases, the First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China
| | - Zhen-Xing Huang
- Department of Endocrinology, Institute of the First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China
| | - Qing-Jie Li
- Department of Cardiology, Institute of Cardiovascular Diseases, the First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China
| | - Rui-Xing Yin
- Department of Cardiology, Institute of Cardiovascular Diseases, the First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China
| | - Quan-Zhen Lin
- Department of Cardiology, Institute of Cardiovascular Diseases, the First Affiliated Hospital, Guangxi Medical University, Nanning 530021, Guangxi, People's Republic of China
| | - Fang Wang
- Department of Cardiology, Affiliated Shanghai First People's Hospital, Shanghai Jiao Tong University, Shanghai, China.
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Kalozoumi G, Tzimas C, Sanoudou D. The expanding role of epigenetics. Glob Cardiol Sci Pract 2012; 2012:7. [PMID: 25610838 PMCID: PMC4239821 DOI: 10.5339/gcsp.2012.7] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2012] [Accepted: 05/20/2012] [Indexed: 12/13/2022] Open
Affiliation(s)
- Georgia Kalozoumi
- Department of Pharmacology, Medical School, University of Athens, Greece
| | - Christos Tzimas
- Molecular Biology Division, Biomedical Research Foundation of the Academy of Athens, Greece
| | - Despina Sanoudou
- Department of Pharmacology, Medical School, University of Athens, Greece ; Molecular Biology Division, Biomedical Research Foundation of the Academy of Athens, Greece
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