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

Graves' disease (GD) is the most frequent cause of hyperthyroidism. Althoug h the etiology is not completely elucidated, there are several lines of evi dence suggesting multifactorial mechanisms. Genetic, constitutional, and en vironmental factors are involved in its pathogenesis. Major histocompatibil ity complex (MHC) class II alleles have been associated with CD in several populations of distinct ethnic backgrounds and there is increasing evidence supporting an association between CD and HLA-DRS in Caucasian populations. The MHC class II alleles were evaluated in 75 Brazilian patients presentin g 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 compa red with controls (37/166, 22.3%, p = 0.009), conferring a relative risk (R R) 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 control s (24/71, 33.8%; p = 0.004), conferring an RR of 3.74 and an EF of 0.351. T he susceptibility conferred by HLA DQA1*0501 was independent of the HLA-DRB 1*0301 allele. On the other hand, the HLA-DQB1*0602 allele was significantl y 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*03 01 and HLA-DQA1*0501 alleles as susceptibility markers for GD, and emphasiz e the participation of the HLA-DQB1*0602 allele as conferring protection ag ainst the development of the disease.