Polymorphisms in the cathepsin L2 (CTSL2) gene show association with type 1 diabetes and early-onset myasthenia gravis
| Autor: | Anne Marit Selvaag, Erik Thorsby, Kjersti S. Rønningen, Tore K Kvien, Berit Flatø, Knut Dahl-Jørgensen, Dag E. Undlien, Geir Joner, Hege Dahlen Sollid, Arthur Melms, Benedicte A. Lie, Eva Tolosa, Marte K. Viken, O Førre |
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| Rok vydání: | 2007 |
| Předmět: |
Adult
Male Candidate gene medicine.medical_specialty Adolescent Cathepsin L Immunology Arthritis Biology medicine.disease_cause Polymorphism Single Nucleotide Linkage Disequilibrium Autoimmunity Internal medicine Cathepsin L2 Myasthenia Gravis medicine Immunology and Allergy Humans Genetic Predisposition to Disease Cathepsin V Age of Onset Child Autoimmune disease Infant General Medicine medicine.disease Cathepsins Myasthenia gravis Cysteine Endopeptidases Endocrinology Diabetes Mellitus Type 1 Rheumatoid arthritis Child Preschool Female |
| Zdroj: | Human immunology. 68(9) |
| ISSN: | 0198-8859 |
| Popis: | Type 1 diabetes (T1D) is an autoimmune disease characterized by loss of beta cells in the pancreas. The CTSL2 gene encodes the cysteine protease cathepsin V involved in antigen presentation in human cortical thymic epithelial cells, and involvement of the protease in autoimmunity has been suggested. This study aimed to evaluate CTSL2 as a candidate gene for T1D, and test whether the gene predisposes more generally to autoimmune diseases. Four polymorphisms aiming at tagging the CTSL2 locus were genotyped in 421 T1D families, and subsequently in 861 rheumatoid arthritis patients, 530 juvenile idiopathic arthritis patients, and 559 controls of Norwegian origin. Additionally, DNA from 83 German myasthenia gravis (MG) patients and 244 controls were investigated. A polymorphism, rs16919034, situated downstream of CTSL2 was associated with T1D (60.8%T, p = 0.008; p(c) = 0.03). An association with early-onset MG (45% in cases vs 36.6% in controls; p = 0.03) was observed for another polymorphism (rs4361859) situated upstream of the gene, but within the same linkage disequilibrium block. No association was observed in rheumatoid arthritis or juvenile idiopathic arthritis. Our findings suggest that the CTSL2 gene is associated with T1D and with early-onset MG. |
| Databáze: | OpenAIRE |
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