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Monocyte Gene-Expression Profiles Associated With Childhood-Onset Type 1 Diabetes and Disease Risk: A Study of Identical Twins

التفاصيل البيبلوغرافية
العنوان: Monocyte Gene-Expression Profiles Associated With Childhood-Onset Type 1 Diabetes and Disease Risk: A Study of Identical Twins
المؤلفون: Harm de Wit, Hemmo A. Drexhage, Huriya Beyan, Roosmarijn C. Drexhage, Roosmarijn C. Padmos, Richard David Leslie, Leonie van der Heul Nieuwenhuijsen, Nanette C. Schloot
المساهمون: Immunology, Internal Medicine, Pediatrics
المصدر: Diabetes, 59(7), 1751-1755. American Diabetes Association Inc.
Diabetes
بيانات النشر: American Diabetes Association Inc., 2010.
سنة النشر: 2010
مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, Biology, Monocytes, SDG 3 - Good Health and Well-being, Diabetes mellitus, Internal medicine, Immunopathology, Internal Medicine, medicine, Diseases in Twins, Cluster Analysis, Humans, Genetic Predisposition to Disease, Gene, Autoimmune disease, Type 1 diabetes, Reverse Transcriptase Polymerase Chain Reaction, Monocyte, Gene Expression Profiling, Twins, Monozygotic, Middle Aged, medicine.disease, Twin study, Gene expression profiling, Endocrinology, medicine.anatomical_structure, Diabetes Mellitus, Type 1, Female, Immunology and Transplantation
الوصف: OBJECTIVE Monocytes in childhood-onset type 1 diabetes show distinct gene expression. We hypothesize that monocyte activation in monozygotic (MZ) twin pairs discordant for childhood-onset type 1 diabetes could reflect distinct stages of the disease process including diabetes susceptibility (differences between twins, both diabetic and nondiabetic, and control subjects) and/or disease progression (differences between diabetic and nondiabetic twins). RESEARCH DESIGN AND METHODS We studied patterns of inflammatory gene expression in peripheral blood monocytes of MZ twin pairs (n = 10 pairs) discordant for childhood-onset type 1 diabetes, normal control twin pairs (n = 10 pairs), and healthy control subjects (n = 51) using quantitative-PCR (Q-PCR). We tested the 24 genes previously observed by whole genome analyses and verified by Q-PCR in autoimmune diabetes and performed a hierarchical cluster analysis. RESULTS Of 24 genes abnormally expressed in childhood-onset type 1 diabetes, we revalidated abnormal expression in 16 of them in diabetic twins including distinct sets of downregulated (P < 0.03) and upregulated (P < 0.02) genes. Of these 16 genes, 13 were abnormally expressed in nondiabetic twins, implicating these genes in diabetes susceptibility (P < 0.044 for all). Cluster analysis of monocyte gene-expression in nondiabetic twins identified two distinct, mutually exclusive clusters, while diabetic twins had a network of positively correlated genes. CONCLUSIONS Patients with childhood-onset type 1 diabetes show abnormal monocyte gene–expression levels with an altered gene–expression network due to gene-environment interaction. Importantly, perturbed gene–expression clusters were also detected in nondiabetic twins, implicating monocyte abnormalities in susceptibility to diabetes.
تدمد: 0012-1797
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fa20b46985f7de572f7aa64ad36b4e92Test
https://pure.eur.nl/en/publications/14cde5a6-6f4d-415e-a796-2ab93a9aa468Test
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....fa20b46985f7de572f7aa64ad36b4e92
قاعدة البيانات: OpenAIRE
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