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  • Title: Association of the HLA-DRB1*0301 and HLA-DQA1*0501 alleles with Graves' disease in a population representing the gene contribution from several ethnic backgrounds.
    Author: Maciel LM, Rodrigues SS, Dibbern RS, Navarro PA, Donadi EA.
    Journal: Thyroid; 2001 Jan; 11(1):31-5. PubMed ID: 11272094.
    Abstract:
    Graves' disease (GD) is the most frequent cause of hyperthyroidism. Although the etiology is not completely elucidated, there are several lines of evidence suggesting multifactorial mechanisms. Genetic, constitutional, and environmental factors are involved in its pathogenesis. Major histocompatibility complex (MHC) class II alleles have been associated with GD in several populations of distinct ethnic backgrounds and there is increasing evidence supporting an association between GD and HLA-DR3 in Caucasian populations. The MHC class II alleles were evaluated in 75 Brazilian patients presenting with GD and in 166 control individuals from the same geographic area. HLA-DRB, DQB, and DQA alleles were identified using polymerase chain reaction (PCR)-amplified DNA hybridized with sequence-specific probes. The HLA-DRB1*0301 allele was significantly increased in patients (34/75, 45.3%) as compared with controls (37/166, 22.3%, p = 0.009), conferring a relative risk (RR) of 2.8 and an etiologic fraction (EF) of 0.287. The HLA-DQA1*0501 allele was also overrepresented in patients (48/71, 67.6%) in relation to controls (24/71, 33.8%; p = 0.004), conferring an RR of 3.74 and an EF of 0.351. The susceptibility conferred by HLA-DQA1*0501 was independent of the HLA-DRB1*0301 allele. On the other hand, the HLA-DQB1*0602 allele was significantly decreased in patients (6/75, 8.0%) in relation to controls (53/166, 31.9%, p = 0.0008), conferring an RR of 0.18 and a preventive fraction of 0.267. Although the Brazilian population comprises individuals of several ethnic backgrounds, these results corroborate the participation of the HLA-DRB1*0301 and HLA-DQA1*0501 alleles as susceptibility markers for GD, and emphasize the participation of the HLA-DQB1*0602 allele as conferring protection against the development of the disease.
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