Homozygosity of the Polymorphism MICA5.1 Identifies Extreme Risk of Progression to Overt Adrenal Insufficiency among 21-Hydroxylase Antibody-Positive Patients with Type 1 Diabetes
| Autor: | Dongmei Miao, Pamela R. Fain, Taylor M. Triolo, Carrie S. Toews, Liping Yu, Taylor K. Armstrong, Peter A. Gottlieb, Marian Rewers, George S. Eisenbarth, Erin E. Baschal, Jennifer M. Barker |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
endocrine system
medicine.medical_specialty endocrine system diseases Genotype Endocrinology Diabetes and Metabolism Clinical Biochemistry Context (language use) Polymerase Chain Reaction Biochemistry Endocrinology Addison Disease immune system diseases Risk Factors Polymorphism (computer science) HLA-DQ Antigens Immunopathology Internal medicine Adrenal insufficiency medicine HLA-DQ beta-Chains Humans Alleles Autoantibodies Type 1 diabetes Polymorphism Genetic business.industry Histocompatibility Antigens Class I Homozygote Biochemistry (medical) Autoantibody nutritional and metabolic diseases Interferon-alpha HLA-DR Antigens medicine.disease Graves Disease Cross-Sectional Studies Diabetes Mellitus Type 1 Addison's disease Disease Progression Original Article Steroid 21-Hydroxylase business HLA-DRB1 Chains Microsatellite Repeats Cohort study |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 94:4517-4523 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jc.2009-1308 |
| Popis: | Context: Autoimmunity associated with Addison’s disease (AD) can be detected by measuring 21-hydroxylase (21OH) autoantibodies. Subjects with type 1 diabetes (T1D) are at increased risk for AD. Genetic factors including HLA-DRB1*0404 and MICA have been associated with AD in populations with and without T1D. Objective: The objective of the study was to examine the effect of the MICA5.1 allele in subjects with 21OH autoantibodies on progression to AD. Design: Two components were used: 1) a cross-sectional study with subjects with AD identified and enrolled from September 1993 to November 2008 and 2) a cohort study prospectively following up patients with T1D who screened positive for 21OH autoantibodies. Setting: Subjects were identified from the Barbara Davis Center and through the National Adrenal Diseases Foundation. Patients: Sixty-three subjects with AD were referred through the National Adrenal Diseases Foundation (AD referrals). Sixty-three subjects with positive 21OH antibodies from the Barbara Davis Center were followed up for progression to AD, and 11 were diagnosed with AD (progressors). Results: Seventy-three percent of progressors (eight of 11) and 57% of AD referrals (36 of 63) were MICA5.1 homozygous (P = ns). Overall, 59% of patients with AD (44 of 74) were MICA5.1/5.1 compared with 17% of nonprogressors (nine of 52) (P < 0.0001) and 19% of normal DR3/4-DQB1*0302 controls (64 of 336) (P < 0.0001). Conclusions: Identifying extreme risk should facilitate monitoring of progression from 21OH antibody positivity to overt AD. The HLA-DR3/0404 genotype defines high-risk subjects for adrenal autoimmunity. MICA5.1/5.1 may define those at highest risk for progression to overt AD, a feature unique to AD and distinct from T1D. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|