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Discerning Genetic Risk for DR3-Associated Endocrine Autoimmunity


New research on genetic risk for DR-3

Celiac.com 08/05/2010 - A myriad of autoimmune disorders including, Addison's disease, type 1 diabetes and celiac disease are closely associated with the HLA-DR3 haplotype. However it is has been hypothesized that alleles of other genes in linkage disequilibrium with HLA-DRB1 also contribute to the diseases.

Researchers at the Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, Aurora, Colorado, conducted a study to characterize major histocompatability complex (MHC) haplotypes which put patients at high risk for Addison's disease.

Between 1992 and 2009, eighty-six Caucasian subjects with 21-hydroxylase autoantibody-positive , nonautoimmune polyendocrine syndrome type 1, were genotyped for JLA-DRB1, HLA-DQB1, MICA, HLA-B, HLA-A and high density MHC single-nucleotide polymorphism analysis for 34.

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Measuring AD and genotype, 97% of the multiplex subjects, 60% of the simplex AD subjects and 13% of the general population control group had both HLA-DR3 and HLA-B8. The study also found that 85% of the AD multiplex subjects, 24% of the simplex patients and 1.5% of the control group subjects presented with DR3/DR4 and B8. Also discovered through this study was that the DR3-B8 haplotype of AD subjects only 47% had HLA-A1, compared to the control subjects at 81% and the type 1 diabetic subjects at 73%.

Researchers of this study concluded that severe risk for Addison's disease, specifically in multiplex families, is connected to haplotypic DR3 variants in specific a part (3.8) though not all of the conserved 3.8.1 haplotype.

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