title: Association of HLA-DR, -DQ genotype and CTLA-4 gene polymorphism with Graves' disease in Japanese children.
abstract: OBJECTIVE
  Childhood onset Graves' disease (GD) has been documented to be clinically distinct from adult onset GD, and an association with the genes encoding HLA and CTLA-4 (cytotoxic T lymphocyte antigen-4) has been reported in both Caucasian and Japanese adult GD patients. The aim of this study was to determine whether HLA-DR, -DQ and CTLA-4 are associated with childhood onset GD in Japanese individuals.
  
  
  METHODS
  We investigated the genotype of HLA class II (DRB1, DQB1) and the A/G transition polymorphism of CTLA-4 exon 1 position 49 in 43 GD patients and in healthy controls for comparison. The CTLA-4 alleles were identified by the polymerase chain reaction (PCR) of genomic DNA and restriction fragment-length polymorphism analysis (PCR-RFLP) with Ita1.
  
  
  RESULTS
  The frequency of both HLA-DRB1*0405 and DQB1*0401 was increased in the patient group (DRB1*0405: 26.7%, p < 0.001; DQB1*0401: 25.6%, p < 0.005) compared with the controls. Patients with GD had a significantly lower frequency of the AA genotype of CTLA-4 than the controls, but there was no difference in allele frequency between the G and A allele.
  
  
  CONCLUSIONS
  the association of HLA-DRB1 and DQB1 genotype with susceptibility to childhood onset GD differs from that in adult onset GD, whereas the association between CTLA-4 gene polymorphism and childhood onset GD is similar to that in adult onset GD in Japanese individuals, but the association is weak.
authors.affiliation: Department of Pediatrics, Tokyo Women's Medical University Daini Hospital, 2-2-10 Nishiogu, Arakawa-ku, Tokyo 116-8567, Japan. iwamapd@dnh.twmu.ac.jp
authors.forename: Saika
authors.initials: S
authors.lastname: Iwama
authors.forename: Ayako
authors.initials: A
authors.lastname: Ikezaki
authors.forename: Noriko
authors.initials: N
authors.lastname: Kikuoka
authors.forename: Hye-Sook
authors.initials: HS
authors.lastname: Kim
authors.forename: Hisafumi
authors.initials: H
authors.lastname: Matsuoka
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Yanagawa
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Sato
authors.forename: Mari
authors.initials: M
authors.lastname: Hoshi
authors.forename: Tateo
authors.initials: T
authors.lastname: Sakamaki
authors.forename: Shigetaka
authors.initials: S
authors.lastname: Sugihara
mesh_terms: D000293:Adolescent; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006111:Graves Disease / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens