Microsatellite Polymorphism of the MHC Class I Chain-Related (MIC-A and MIC-B) Genes Marks the Risk for Autoimmune Addison’s Disease

• DOI: 10.1210/jcem.84.10.6069
• Publication Date: 2014-01-08T17:03:58Z
• Authors: Giovanni Gambelunghe; Alberto Falorni; Mehran Ghaderi; Stefano Laureti; Cristina Tortoioli; Fausto Santeusanio; Paolo Brunetti; Carani B. Sanjeevi
• Keywords: Adult; Male; Adolescent; Genotype; Genes, MHC Class I; HLA-DQ alpha-Chains; Autoimmune Diseases; 03 medical and health sciences; 0302 clinical medicine; Addison Disease; HLA-DQ Antigens; HLA-DQ beta-Chains; Humans; Child; Aged; Polymorphism, Genetic; Histocompatibility Antigens Class I; HLA-DR Antigens; Middle Aged; 3. Good health; Female; HLA-DRB1 Chains; Microsatellite Repeats

Abstract The major histocompatibility complex class I chain-related MIC-A and MIC-B genes are located on chromosome 6 between the leucocyte antigen (HLA)-B B-associated transcript genes. presence of 21-hydroxylase autoantibodies is a sensitive specific marker autoimmune Addison’s disease. We studied polymorphism exon 5 gene, intron 1 HLA-DRB1, -DQA1, -DQB1 in 28 (21-hydroxylase autoantibody positive) disease patients 75 healthy subjects from central Italy. MIC-A5.1 allele was significantly more frequent (79%) than (36%) [odds ratio (OR) = 6.52, corrected P (Pc) 0.0015], whereas MIC-A6 reduced affected (15% vs. 56%, OR 0.13, Pc 0.002). A5.1/A5.1 genotype had an for as high 18.0 absolute risk per 1131. In MIC-A5.1, MICB-CA-25 increased (25% 4%, 8.0, 0.0039, 0.047). MICB-CA-17 absent patients, but present 25% individuals (OR 0.10, 0.0025, 0.03). Among HLA-DR -DQ haplotypes, only DRB1*03-DQA1*0501-DQB1*0201 (DR3/DQ2) subjects, MIC-A5.1. frequency HLA-DR3-DQ2. Our study demonstrates that susceptibility to linked microsatellite 5.1 both HLA-DR3/DQ2 necessary confer genetic