Association Analysis of the Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) and Autoimmune Regulator-1 (AIRE-1) Genes in Sporadic Autoimmune Addison’s Disease1
| Autor: | R. A. James, P. H. Baylis, Petros Perros, E. T. Young, William F. Kelly, Steve Ball, Pat Kendall-Taylor, Shs Pearce, Bijay Vaidya, D. R. Geatch, David H. Carr, Anthony P. Weetman, Helen Imrie, E.H. Kemp, S. J. Hurel |
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| Rok vydání: | 2000 |
| Předmět: |
Genetics
medicine.medical_specialty biology Endocrinology Diabetes and Metabolism Biochemistry (medical) Clinical Biochemistry Gene Abnormality Autoimmune polyendocrinopathy Autoimmune regulator Major histocompatibility complex Biochemistry Endocrinology Antigen CTLA-4 Internal medicine Immunology Genotype medicine biology.protein Allele |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 85:688-691 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jcem.85.2.6369 |
| Popis: | Although autoimmune Addison's disease (AAD) may occur as a component of the monogenic autoimmune polyendocrinopathy type 1 syndrome (APS1), it is most commonly found as an isolated disorder or associated with the autoimmune polyendocrinopathy type 2 syndrome (APS2). It is likely that sporadic (non-APS1) AAD is inherited as a complex trait; however, apart from the major histocompatibility complex, the susceptibility genes remain unknown. We have examined polymorphisms at two non-major histocompatibility complex candidate susceptibility loci in sporadic (non-APS1) AAD: the cytotoxic T lymphocyte antigen-4 (CTLA-4) gene and the autoimmune regulator (AIRE-1) gene. DNA samples from AAD subjects (n = 90) and local controls (n = 144 for CTLA-4; n = 576 for AIRE-1) were analyzed for the CTLA-4A/G polymorphism in exon 1 of the CTLA-4 gene and for the common mutant AIRE-1 allele (964de113) in United Kingdom subjects with APS1, by using the restriction enzymes Bst7II and BsrBI, respectively. There was an association of the G allele at CTLA-4A/G in AAD subjects (P = 0.008 vs. controls), which was stronger in subjects with AAD as a component of APS2 than in subjects with isolated AAD. In contrast, the mutant AIRE-1 964del13 allele was carried in one each of the 576 (0.2%) control subjects and the 90 (1.1%) AAD subjects as a heterozygote (P = 0.254, not significant), suggesting that this common AIRE-1 gene abnormality does not have a major role in sporadic (non-APS1) AAD. |
| Databáze: | OpenAIRE |
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