Association of major histocompatibility complex class II alleles with graves disease in Brazilian patients

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. Genetical, constitutional and environmental factors are involved in the pathogenesis. Major Histocompatibility Complex (MHC) Class II alleles have been associated with GD in several populations of distinct ethnic background and there is increasing evidence supporting an association between GD and HLA-DR3 in Caucasian populations. The MHC Classe II alleles were evaluated in our highly miscigenated population with GD and in control individuals of the same geographic area. MHC Class II genes were identified using PCR-amplified DNA hybridized with sequence-specific probes. HLA DRB1*0301 allele was significantly increased in patients (44,7%) as compared with controls (22,3%, pc=0.0068), conferring a Relative Risk (RR) of 4.1 and an Etiologic Fraction of 28.7. HLA-DQB1*0602 allele was significantly decreased in patients (pc=0.00062), conferring an RR and a Preventive Fraction of 1.8 and 26.7, respectively. Although the Brazilian population is highly miscegenated, the results corroborated the participation of the allele HLA-DRB1*0301 as a susceptibility marker to GD. In contrast, the protection conferred by the HLA-DQB1*0602 allele seems to be peculiar to Brazilian patients.