title: Primary role of the HLA class II DRB1*0301 allele in Graves disease.
abstract: The association of the Graves disease (GD) with HLA DR3 and DQA1*0501 in Caucasians has been described previously. From these studies it could not be determined whether one specific locus was primarily involved. Using a case-control study design, we have examined the role of HLA class II gene polymorphisms in the predisposition for GD in a group of Belgian subjects. We demonstrated that both DRB1*0301 and DQA1*0501 alleles conferred significant susceptibility in the DRB1*0301-DQA1*0501 haplotype. The DRB1*0301 allele was the primary susceptibility allele for GD, however, because the susceptibility provided by DQA1*0501 was most likely due to it being in linkage disequilibrium with DRB1*0301. The DRB1*0701/x and DQA1*0201/x genotypes and the DRB1*0701-DQA1*0201 haplotype provided protection with an equal RR of 0.29. Predictive value calculations showed that testing for DRB1*0301 gave the highest positive predictive value for GD in females and males. This was, however, 10 times higher in females and predicted a 3.63% risk for a random female to develop GD.
authors.affiliation: Center for Human Genetics, University of Leuven, Leuven, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Zamani
authors.forename: M
authors.initials: M
authors.lastname: Spaepen
authors.forename: M
authors.initials: M
authors.lastname: Bex
authors.forename: R
authors.initials: R
authors.lastname: Bouillon
authors.forename: J J
authors.initials: JJ
authors.lastname: Cassiman
mesh_terms: D000483:Alleles; D004247:DNA / Q000032:analysis; D004198:Disease Susceptibility; D005260:Female; D005838:Genotype; D006111:Graves Disease / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control; D006684:HLA-DR Antigens / Q000145:classification / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011379:Prognosis; D018570:Risk Assessment; D012680:Sensitivity and Specificity
chemical_list: D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen; D004247:DNA