RESUMO
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 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). 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 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.
Assuntos
Predisposição Genética para Doença , Antígenos HLA-DR/genética , Poliendocrinopatias Autoimunes/genética , Adolescente , Adulto , Idade de Início , Alelos , Criança , Feminino , Frequência do Gene , Genótipo , Alemanha/epidemiologia , Antígenos HLA-DQ/genética , Cadeias beta de HLA-DQ , Cadeias HLA-DRB1 , Antígenos de Histocompatibilidade Classe I/genética , Humanos , Masculino , Pessoa de Meia-Idade , Poliendocrinopatias Autoimunes/epidemiologia , Reação em Cadeia da Polimerase , Polimorfismo GenéticoRESUMO
BACKGROUND: The autoimmune thyropathies Graves' disease (GD) and Hashimoto's thyroiditis (HT) have multiple genetic and environmental backgrounds. Allele alterations of immune genes might contribute to the development of autoimmunity. PATIENTS AND METHODS: This study determined a triplet short tandem repeat (STR) polymorphism in the transmembrane region of the major histocompatibility complex (MHC) class I chain-related gene A (MICA) of 391 subjects (129 patients with GD, 56 patients with HT, and 206 healthy controls). Five common alleles have been reported for MICA. Genotypes were determined by fragment-length analysis in an ABI PRISM automatic sequencer. RESULTS: The prevalence of the MICA allele A9 was raised in patients with HT compared to controls (22.4% vs. 13.1%; p = 0.016; Fisher's exact test). For MICA, the genotype A5.1/A5.1 occurred more frequently in patients with GD than in controls (24.0% vs. 13.6%, odds ratio [OR] = 2.0, 95% confidence interval [95% CI] = 1.1-3.6; p = 0.018). The genotype MICA A6/A9 was decreased in patients with GD in contrast to controls (1.6% vs. 5.8%, OR = 0.2, 95% CI = 0.6-1.2; p = 0.089). Also, in patients with HT, the genotype A5.1/A9 was increased compared to controls (23.2% vs. 10.7%, OR = 2.5, 95% CI = 1.2-5.4; p = 0.025). CONCLUSION: The genotype MICA A5.1/A5.1 may be regarded as a risk factor for the development of GD. Also, the MICA genotype A5.1/A9 could raise the risk for acquiring HT. Finally, the genotype MICA A6/A9 could be seen as a protective factor against GD.
