title: The human leukocyte antigen HLA DRB3*020/DQA1*0501 haplotype is associated with Graves' disease in African Americans.
abstract: Information on genetic susceptibility to Graves' disease in African Americans is limited. We studied DRB1, DQB1, DRB3 subtypes, DQA1*0501, DQA1*0201, and CTLA-4 polymorphisms in 49 African American patients with adult onset Graves' disease and 47 racially-matched controls using PCR-based sequence-specific priming methods. There were no significant differences in DRB1 or DQB1 allelic frequencies or CTLA-4 polymorphisms between patients and controls. However, we found that the frequency of DRB3 was significantly increased in the patients (75.5% vs. 57.4%, P = 0.006, X2 = 3.52), especially for the DRB3*0202 subtype (53.1% vs. 23.4, P = 0.003, X2 = 8.91). In this one respect, the finding was in concordance with our previous observations in Caucasian patients with adult-onset Graves' disease. In addition, whereas the frequency of DQA1*0501 was increased (P = 0.018, X2 = 5.63) in our patients, the haplotype of DRB3/DQA1*0501, or DRB3*0202/DQA1*0501 was found to be more strongly associated (P = 0.008, X2 = 7.0; P = 0.0008, X2 = 11.34, respectively). These data suggest that DRB3*0202, particularly when found with DQA1*0501 in a haplotype is a susceptible gene(s) for Graves' disease in adult African Americans. Considering these data with those in Caucasian patients, our results would suggest that the primary Graves susceptible locus is likely DRB3 and not DRB1.
authors.affiliation: The Research Institute for Children, Children's Hospital, Harahan, Louisiana 70123, USA.
authors.forename: Q Y
authors.initials: QY
authors.lastname: Chen
authors.forename: D
authors.initials: D
authors.lastname: Nadell
authors.forename: X Y
authors.initials: XY
authors.lastname: Zhang
authors.forename: A
authors.initials: A
authors.lastname: Kukreja
authors.forename: Y J
authors.initials: YJ
authors.lastname: Huang
authors.forename: J
authors.initials: J
authors.lastname: Wise
authors.forename: F
authors.initials: F
authors.lastname: Svec
authors.forename: R
authors.initials: R
authors.lastname: Richards
authors.forename: K E
authors.initials: KE
authors.lastname: Friday
authors.forename: A
authors.initials: A
authors.lastname: Vargas
authors.forename: R
authors.initials: R
authors.lastname: Gomez
authors.forename: S
authors.initials: S
authors.lastname: Chalew
authors.forename: M S
authors.initials: MS
authors.lastname: Lan
authors.forename: Y
authors.initials: Y
authors.lastname: Tomer
authors.forename: N K
authors.initials: NK
authors.lastname: Maclaren
mesh_terms: D000069594:Abatacept; D000328:Adult; D000483:Alleles; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics; D044383:Black People / Q000235:genetics*; D060908:CTLA-4 Antigen; D005260:Female; D005787:Gene Frequency; D006111:Graves Disease / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D059826:HLA-DRB3 Chains; D059845:HLA-DRB4 Chains; D006239:Haplotypes; D006801:Humans; D018796:Immunoconjugates; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D001741:Black or African American
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D059826:HLA-DRB3 Chains; D059845:HLA-DRB4 Chains; D018796:Immunoconjugates; D000069594:Abatacept