Association of HLA-DR, -DQ genotype and CTLA-4 gene polymorphism with Graves' disease in Japanese children.
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.
Iwama
Saika
S
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
Ikezaki
Ayako
A
Kikuoka
Noriko
N
Kim
Hye-Sook
HS
Matsuoka
Hisafumi
H
Yanagawa
Tatsuo
T
Sato
Hirokazu
H
Hoshi
Mari
M
Sakamaki
Tateo
T
Sugihara
Shigetaka
S
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
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens