title: HLA-DRB3 gene alleles in Caucasian patients with Graves' disease.
abstract: Graves' disease (GD) is a human leukocyte antigen (HLA) linked organ-specific autoimmune disease. In German GD patients the disease is associated with HLA specificities of the HLA-DRw52 family (HLA-DR3, -DR5, and DR6; HLA-DRB3 positive HLA haplotypes). Recently, a strong association with a HLA-DRB3 restriction fragment length polymorphism gene has been described. To study HLA-DRB3 alleles and their association with the disease, a large cohort of controls (n = 3724) and GD patients (n = 304) was analyzed. HLA-DR allelic combinations revealed an increase in HLA-DR3/DR5 heterozygous patients (relative risk 2.9; P < 0.001). HLA-DRB3 alleles, as defined by DNA typing in HLA-DR matched groups revealed a significant increase in DRB3*0101 homozygosity (relative risk 17.5; P < 0.001) in HLA-DR3 homozygous patients. In GD patients with ophthalmopathy (grade II or higher, according to Werner) DRB3*0101/*0202 heterozygosity revealed an increased relative risk of 5.5 (P < 0.001). Non-HLA-DR3 homozygous, DRB3*0101/*0202 heterozygous patients were at the highest risk for endocrine ophthalmopathy (relative risk 10; P < 0.001). Our data, based on DNA typing methods of HLA-D genes, provide evidence that the susceptibility is strongly associated with HLA-DRB3 genes.
authors.affiliation: Klinikum der Johann Wolfgang Goethe-Universität, Zentrum der Inneren Medizin, Frankfurt, Main.
authors.forename: B O
authors.initials: BO
authors.lastname: Boehm
authors.forename: P
authors.initials: P
authors.lastname: Kühnl
authors.forename: B J
authors.initials: BJ
authors.lastname: Manfras
authors.forename: M
authors.initials: M
authors.lastname: Chen
authors.forename: J C
authors.initials: JC
authors.lastname: Lee
authors.forename: G
authors.initials: G
authors.lastname: Holzberger
authors.forename: S
authors.initials: S
authors.lastname: Seidl
authors.forename: E
authors.initials: E
authors.lastname: Schifferdecker
authors.forename: P M
authors.initials: PM
authors.lastname: Schumm-Draeger
authors.forename: K H
authors.initials: KH
authors.lastname: Usadel
mesh_terms: D000483:Alleles; D001483:Base Sequence; D015415:Biomarkers / Q000097:blood; D004247:DNA / Q000032:analysis; D006111:Graves Disease / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D059826:HLA-DRB3 Chains; D006579:Heterozygote; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D012307:Risk Factors; D012698:Serologic Tests; D044465:White People / Q000235:genetics*
chemical_list: D015415:Biomarkers; D006684:HLA-DR Antigens; D059826:HLA-DRB3 Chains; D004247:DNA