Receptor for advanced glycation end-products (RAGE) provides a link between genetic susceptibility and environmental factors in type 1 diabetes
| العنوان: | Receptor for advanced glycation end-products (RAGE) provides a link between genetic susceptibility and environmental factors in type 1 diabetes |
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| المؤلفون: | Felicia Y. T. Yap, Karly C. Sourris, Sofianos Andrikopoulos, Olli Simell, Jenny Söderlund, Carol Forsblom, Maija Wessman, Robyn Maree Slattery, Melinda T. Coughlan, Per-Henrik Groop, Josephine M. Forbes, Jorma Ilonen, Mark E. Cooper, Shane T. Grey, Hiroshi Yamamoto, Riitta Veijola, Mikael Knip, Angelika Bierhaus |
| المصدر: | Diabetologia. 54:1032-1042 |
| بيانات النشر: | Springer Science and Business Media LLC, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Adult, Male, Genotype, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Receptor for Advanced Glycation End Products, Enzyme-Linked Immunosorbent Assay, 030209 endocrinology & metabolism, Biology, medicine.disease_cause, Autoimmunity, Mice, 03 medical and health sciences, 0302 clinical medicine, Mice, Inbred NOD, Glycation, Internal Medicine, medicine, Genetic predisposition, Animals, Humans, Genetic Predisposition to Disease, Receptors, Immunologic, Receptor, 030304 developmental biology, 0303 health sciences, Type 1 diabetes, Polymorphism, Genetic, Reverse Transcriptase Polymerase Chain Reaction, Insulin, Human physiology, Middle Aged, medicine.disease, Immunohistochemistry, Diabetes Mellitus, Type 1, Immunology, Alagebrium Chloride, Female |
| الوصف: | This group of studies examines human genetic susceptibility conferred by the receptor for advanced glycation end-products (RAGE) in type 1 diabetes and investigates how this may interact with a western environment.We analysed the AGER gene, using 13 tag SNPs, in 3,624 Finnish individuals from the FinnDiane study, followed by AGER associations with a high risk HLA genotype (DR3)-DQA1*05-DQB1*02/DRB1*0401-DQB1*0302 (n = 546; HLA-DR3/DR4), matched in healthy newborn infants from the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Study (n = 373) using allelic analysis. We also studied islets and circulating RAGE in NODLt mice.The rs2070600 and rs17493811 polymorphisms predicted increased risk of type 1 diabetes, whereas the rs9469089 SNP was related to decreased risk, on a high risk HLA background. Children from the DIPP study also showed a decline in circulating soluble RAGE levels, at seroconversion to positivity for type 1 diabetes-associated autoantibodies. Islet RAGE and circulating soluble RAGE levels in prediabetic NODLt mice decreased over time and were prevented by the AGE lowering therapy alagebrium chloride. Alagebrium chloride also decreased the incidence of autoimmune diabetes and restored islet RAGE levels.These studies suggest that inherited AGER gene polymorphisms may confer susceptibility to environmental insults. Declining circulating levels of soluble RAGE, before the development of overt diabetes, may also be predictive of clinical disease in children with high to medium risk HLA II backgrounds and this possibility warrants further investigation in a larger cohort. |
| تدمد: | 1432-0428 0012-186X 1749-3811 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c1a0b46239c76653dcb164cd60d6a01dTest https://doi.org/10.1007/s00125-011-2058-zTest |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....c1a0b46239c76653dcb164cd60d6a01d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14320428 0012186X 17493811 |
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