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Early onset of polyglandular failure is associated with HLA-DRB1*03

M Dittmar, Department of Medicine I, Gutenberg University, Mainz, Germany
M Ide, Mainz, Germany
M Wurm, Mainz, Germany
G Kahaly, Mainz, Germany

Correspondence: George J. Kahaly, Email: gkahaly{at}mail.uni-mainz.de

Abstract

Objectives: Polyglandular failure or autoimmunity (PGA) involves at least two endocrine diseases. Several genes may play a role in its etiology. This study analyzed (1) whether HLA-DRB1, HLA-DQB1 and MICA polymorphisms are associated in PGA and (2) whether PGA patients display stronger associations with these immune genes than patients with monoglandular autoimmunity (MGA). Design: Association study. Methods: HLA-DRB1, HLA-DQB1, and MICA alleles were analyzed in 73 patients with PGA, 283 with MGA, and 206 healthy controls. The HLA-DRB1 and DQB1 polymorphisms were determined with PCR-amplified DNA being hybridized with sequence specific oligonucleotide probes (PCR-SSO). MICA microsatellites were typed by PCR amplification and fragment size analysis on a DNA sequencer. Results: HLA-DRB1*03 was strongly increased in patients with PGA (50.7%) vs. both controls (21.8%, Pc<0.0001; RR = 2.32, 95% CI =1.62-3.33) and MGA (11.4%, Pc<0.0001). HLA-DRB1*03 was highly prevalent in PGA patients with early vs. late disease onset (P<0.05, logistic regression analysis). HLA-DRB1*04 allele carriers were more present in PGA vs. controls (53.4% vs. 22.4%, Pc<0.0001, RR = 2.38, 95% CI = 1.68-3.38). Further, HLA-DQB1*02 was increased in PGA vs. controls (Pc<0.01), whereas HLA-DQB1*06 was decreased (Pc<0.001). Patients with PGA showed more MIC A5.1 and less MIC A6 allele carriers than controls (n.s.). Presence of the MIC A5.1 allele was not associated with the HLA-DRB1*03 or HLA-DQB1 alleles. Conclusions: HLA-DRB1*03 is a stronger genetic marker in PGA than in MGA, foremost in those with early disease onset.

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