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J Clin Endocrinol Metab. 2012 Aug;97(8):E1573-8. doi: 10.1210/jc.2011-2824. Epub 2012 Jun 20.

Genetic determinants of 21-hydroxylase autoantibodies amongst patients of the Type 1 Diabetes Genetics Consortium.

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  • 1Barbara Davis Center for Childhood Diabetes, Aurora, Colorado 80045, USA.



Autoantibodies to 21-hydroxylase (21OH-AA) precede the onset of autoimmune Addison's disease (AD) and are found in 1.5% of individuals with type 1 diabetes mellitus (T1DM). The greatest genetic risk for both disorders is found in the major histocompatibility complex (MHC), suggesting a common pathophysiology between AD and T1DM. Screening for 21OH-AA in newly diagnosed T1DM patients is a valuable prognostic tool, made stronger when MHC genotype is considered.


The Type 1 Diabetes Genetics Consortium has collected genotype data in T1DM subjects with tissue-specific autoantibody typing. Genotype and phenotype data in individuals positive and negative for 21OH-AA are compared.


Major genetic risk for 21OH-AA is in the MHC haplotypes DRB1*04-DQB1*0302 (primarily DRB1*0404) and DRB1*0301-DQB1*0201. Protective effects in class II MHC haplotypes DRB1*0101-DQB1*0501 and DRB1*0701-DQB1*0202 also were detected. There is no difference in the presence of HLA-B15 and little difference in the presence of HLA-B8 (after class II effects are accounted for) in T1DM patients with 21OH-AA compared with known associations (HLA-B8 positive and HLA-B15 negative) in AD.


In 21OH-AA(+) subjects, genetic risk is found mainly in MHC class II haplotypes DR3 and DR4 but not class I alleles (HLA-B8 or HLA-B15). This suggests a difference between autoantibody formation (class II dependent) and progression to overt disease (class I dependent) in AD.

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