Early onset of polyglandular failure is associated with HLA-DRB1*03.
OBJECTIVE
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 MHC class I chain-related gene A (MICA) polymorphisms are associated in PGA and 2) whether PGA patients display stronger associations with these immune genes than patients with monoglandular autoimmunity (MGA).


METHODS
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 HLA-DQB1 polymorphisms were determined with PCR-amplified DNA being hybridized with PCR-sequence-specific oligonucleotide probes. 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%) versus both controls (21.8%, P(c)<0.0001; RR=2.32, 95% CI=1.62-3.33) and MGA (11.4%, P(c)<0.0001). HLA-DRB1*03 was highly prevalent in PGA patients with early versus late disease onset (P<0.05, logistic regression analysis). HLA-DRB1*04 allele carriers were more present in PGA versus controls (53.4% vs 22.4%, P(c)<0.0001, RR=2.38, 95% CI=1.68-3.38). Further, HLA-DQB1*02 was increased in PGA versus controls (P(c)<0.01), whereas HLA-DQB1*06 was decreased (P(c)<0.001). Patients with PGA showed more MIC A5.1 and less MIC A6 allele carriers than controls (NS). 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.
Dittmar
Manuela
M
Department of Medicine I, Gutenberg University Hospital, Mainz 55101, Germany.
Ide
Maximilian
M
Wurm
Michael
M
Kahaly
George J
GJ
D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000483:Alleles; D002648:Child; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006683:HLA-DQ Antigens / Q000235:genetics; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D016884:Polyendocrinopathies, Autoimmune / Q000453:epidemiology / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D015395:Histocompatibility Antigens Class I; C099187:MHC class I-related chain A