Haplotype analysis discriminates genetic risk for DR3-associated endocrine autoimmunity and helps define extreme risk for Addison's disease.

The Journal of Clinical Endocrinology and Metabolism
Peter BakerG S Eisenbarth

Abstract

Multiple autoimmune disorders (e.g. Addison's disease, type 1 diabetes, celiac disease) are associated with HLA-DR3, but it is likely that alleles of additional genes in linkage disequilibrium with HLA-DRB1 contribute to disease. The objective of the study was to characterize major histocompatability complex (MHC) haplotypes conferring extreme risk for autoimmune Addison's disease (AD). Eighty-six 21-hydroxylase autoantibody-positive, nonautoimmune polyendocrine syndrome type 1, Caucasian individuals collected from 1992 to 2009 with clinical AD from 68 families (12 multiplex and 56 simplex) were genotyped for HLA-DRB1, HLA-DQB1, MICA, HLA-B, and HLA-A as well as high density MHC single-nucleotide polymorphism (SNP) analysis for 34. AD and genotype were measured. Ninety-seven percent of the multiplex individuals had both HLA-DR3 and HLA-B8 vs. 60% of simplex AD patients (P = 9.72 × 10(-4)) and 13% of general population controls (P = 3.00 × 10(-19)). The genotype DR3/DR4 with B8 was present in 85% of AD multiplex patients, 24% of simplex patients, and 1.5% of control individuals (P = 4.92 × 10(-191)). The DR3-B8 haplotype of AD patients had HLA-A1 less often (47%) than controls (81%, P = 7.00 × 10(-5)) and type 1 diabetes patient...Continue Reading

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Citations

Jun 29, 2013·Diabetes Technology & Therapeutics·Marian Rewers
May 14, 2011·The Journal of Clinical Endocrinology and Metabolism·Peter R BakerGeorge S Eisenbarth
Jun 23, 2012·The Journal of Clinical Endocrinology and Metabolism·Peter BakerGeorge Eisenbarth
Jul 7, 2012·The Journal of Clinical Endocrinology and Metabolism·Simon H S PearceBijay Vaidya
Dec 10, 2013·BioMed Research International·Wen-Pei ChenYaw-Ling Lin
Sep 25, 2014·European Journal of Endocrinology·Ingeborg BrønstadAnette Susanne Bøe Wolff
Nov 10, 2011·Clinical Endocrinology·Peter R BakerJennifer M Barker
Dec 7, 2018·The Journal of Clinical Endocrinology and Metabolism·Brigitte K FleschGeorge J Kahaly
Nov 5, 2013·The Journal of Clinical Endocrinology and Metabolism·B K FleschG J Kahaly
Apr 11, 2018·Annales d'endocrinologie·Alexander HellesenEystein S Husebye

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