caa a22 4500 397573529 CHVBK 20180308164848.0 cr unu---uuuuu 161202e199607 xx s 000 0 eng 10.1093/hmg/5.7.1075 doi (NATIONALLICENCE)oxford-10.1093/hmg/5.7.1075 The CTLA-4 Gene Region of Chromosome 2q33 Is Linked to, and Associated with, Type 1 Diabetes [Elektronische Daten] [Lorenza Nisticò, Raffaella Buzzetti, Lynn E. Pritchard, Bart Van der Auwera, Claudio Giovannini, Emanuele Bosi, Maria Teresa Martinez Larrad, Manuel Serrano Rios, C. C. Chow, Clive S. Cockram, Karen Jacobs, Catherine Mijovic, Stephen C. Bain, Anthony H. Barnett, Christina L. Vandewalle, Frans Schuit, Frans K. Gorus, Roberto Tosi, Paolo Pozzilli, John A. Todd] Susceptibility to autoimmune insulin-dependent (type 1) diabetes mellitus is determined by a combination of environmental and genetic factors, which include variation in MHC genes on chromosome 6p21 (IDDM1) and the insulin gene on chromosome 11p15 (IDDM2). However, linkage to IDDM1 and IDDM2 cannot explain the clustering of type 1 diabetes in families, and a role for other genes is inferred. In the present report we describe linkage and association of type 1 diabetes to the CTLA-4 gene (cytotoxic T lymphocyte associated-4) on chromosome 2q33 (designated IDDM12). CTLA-4 is a strong candidate gene for T cell-mediated autoimmune disease because it encodes a T cell receptor that mediates T cell apoptosis and is a vital negative regulator of T cell activation. In addition, we provide supporting evidence that CTLA-4 is associated with susceptibility to Graves' disease, another organ-specific autoimmune disease. © 1996 Oxford University Press Nisticò Lorenza Endocrinologia, Istituto Clinica Medica II, University of Rome ‘La Sapienza', Viale de Policlinico, 151, 00161 Rome, Italy aut Buzzetti Raffaella Endocrinologia, Istituto Clinica Medica II, University of Rome ‘La Sapienza', Viale de Policlinico, 151, 00161 Rome, Italy aut Pritchard Lynn E. The Wellcome Trust Centre for Human Genetics, Nuffield Department of Surgery, University of Oxford, Windmill Road, Headington, Oxford OX3 7BN, UK aut Van der Auwera Bart Department of Biochemistry, Diabetes Research Centre, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, Belgium aut Giovannini Claudio Endocrinologia, Istituto Clinica Medica II, University of Rome ‘La Sapienza', Viale de Policlinico, 151, 00161 Rome, Italy aut Bosi Emanuele Department of Internal Medicine, Istituto Scientifico San Raffaele, University of Milan, Milan, Italy aut Martinez Larrad Maria Teresa Facultad de Medicina, Universidad Complutense, Madrid, Spain aut Serrano Rios Manuel Facultad de Medicina, Universidad Complutense, Madrid, Spain aut Chow C. C. Department of Medicine, The Chinese University of Hong Kong, Hong Kong aut Cockram Clive S. Department of Medicine, The Chinese University of Hong Kong, Hong Kong aut Jacobs Karen Department of Medicine, University of Birmingham and Birmingham Heartlands Hospital, Birmingham B9 5SS, UK aut Mijovic Catherine Department of Medicine, University of Birmingham and Birmingham Heartlands Hospital, Birmingham B9 5SS, UK aut Bain Stephen C. Department of Medicine, University of Birmingham and Birmingham Heartlands Hospital, Birmingham B9 5SS, UK aut Barnett Anthony H. Department of Medicine, University of Birmingham and Birmingham Heartlands Hospital, Birmingham B9 5SS, UK aut Vandewalle Christina L. Department of Metabolism and Endocrinology, Diabetes Research Centre, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, Belgium aut Schuit Frans Department of Biochemistry, Diabetes Research Centre, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, Belgium aut Gorus Frans K. Department of Metabolism and Endocrinology, Diabetes Research Centre, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, Belgium aut Tosi Roberto Department of Immunobiology, Institute of Cell Biology, Consiglio Nazionale delle Ricerche, viale Marx 43, Rome 00137, Italy aut Pozzilli Paolo Endocrinologia, Istituto Clinica Medica II, University of Rome ‘La Sapienza', Viale de Policlinico, 151, 00161 Rome, Italy aut Todd John A. The Wellcome Trust Centre for Human Genetics, Nuffield Department of Surgery, University of Oxford, Windmill Road, Headington, Oxford OX3 7BN, UK aut Human Molecular Genetics Oxford University Press 5/7(1996-07), 1075-1080 0964-6906 5:7<1075 1996 5 hmg https://doi.org/10.1093/hmg/5.7.1075 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/hmg/5.7.1075 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Nisticò Lorenza Endocrinologia, Istituto Clinica Medica II, University of Rome ‘La Sapienza', Viale de Policlinico, 151, 00161 Rome, Italy aut NATIONALLICENCE 700 1- Buzzetti Raffaella Endocrinologia, Istituto Clinica Medica II, University of Rome ‘La Sapienza', Viale de Policlinico, 151, 00161 Rome, Italy aut NATIONALLICENCE 700 1- Pritchard Lynn E. The Wellcome Trust Centre for Human Genetics, Nuffield Department of Surgery, University of Oxford, Windmill Road, Headington, Oxford OX3 7BN, UK aut NATIONALLICENCE 700 1- Van der Auwera Bart Department of Biochemistry, Diabetes Research Centre, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, Belgium aut NATIONALLICENCE 700 1- Giovannini Claudio Endocrinologia, Istituto Clinica Medica II, University of Rome ‘La Sapienza', Viale de Policlinico, 151, 00161 Rome, Italy aut NATIONALLICENCE 700 1- Bosi Emanuele Department of Internal Medicine, Istituto Scientifico San Raffaele, University of Milan, Milan, Italy aut NATIONALLICENCE 700 1- Martinez Larrad Maria Teresa Facultad de Medicina, Universidad Complutense, Madrid, Spain aut NATIONALLICENCE 700 1- Serrano Rios Manuel Facultad de Medicina, Universidad Complutense, Madrid, Spain aut NATIONALLICENCE 700 1- Chow C. C. Department of Medicine, The Chinese University of Hong Kong, Hong Kong aut NATIONALLICENCE 700 1- Cockram Clive S. Department of Medicine, The Chinese University of Hong Kong, Hong Kong aut NATIONALLICENCE 700 1- Jacobs Karen Department of Medicine, University of Birmingham and Birmingham Heartlands Hospital, Birmingham B9 5SS, UK aut NATIONALLICENCE 700 1- Mijovic Catherine Department of Medicine, University of Birmingham and Birmingham Heartlands Hospital, Birmingham B9 5SS, UK aut NATIONALLICENCE 700 1- Bain Stephen C. Department of Medicine, University of Birmingham and Birmingham Heartlands Hospital, Birmingham B9 5SS, UK aut NATIONALLICENCE 700 1- Barnett Anthony H. Department of Medicine, University of Birmingham and Birmingham Heartlands Hospital, Birmingham B9 5SS, UK aut NATIONALLICENCE 700 1- Vandewalle Christina L. Department of Metabolism and Endocrinology, Diabetes Research Centre, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, Belgium aut NATIONALLICENCE 700 1- Schuit Frans Department of Biochemistry, Diabetes Research Centre, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, Belgium aut NATIONALLICENCE 700 1- Gorus Frans K. Department of Metabolism and Endocrinology, Diabetes Research Centre, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, Belgium aut NATIONALLICENCE 700 1- Tosi Roberto Department of Immunobiology, Institute of Cell Biology, Consiglio Nazionale delle Ricerche, viale Marx 43, Rome 00137, Italy aut NATIONALLICENCE 700 1- Pozzilli Paolo Endocrinologia, Istituto Clinica Medica II, University of Rome ‘La Sapienza', Viale de Policlinico, 151, 00161 Rome, Italy aut NATIONALLICENCE 700 1- Todd John A. The Wellcome Trust Centre for Human Genetics, Nuffield Department of Surgery, University of Oxford, Windmill Road, Headington, Oxford OX3 7BN, UK aut NATIONALLICENCE 773 0- Human Molecular Genetics Oxford University Press 5/7(1996-07), 1075-1080 0964-6906 5:7<1075 1996 5 hmg Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford