The HLA-DRB1 gene and Graves disease in Taiwanese children: a case-control and family-based study.
Graves disease (GD) is an autoimmune thyroid disease with a female preponderance and a wide range of ages at onset, and human leukocyte antigen (HLA) gene plays a primary role in the susceptibility to GD. We aim to investigate the associations between HLA-DRB1 alleles and Taiwanese children with GD by both case-control and family-based studies. A total of 241 unrelated children with GD, 539 healthy controls, 115 trios of affected patients and their parents, and 121 trios of unaffected siblings and their parents were recruited. HLA-DRB1 genotyping was performed by polymerase chain reaction and sequence-based typing assays. We found that DRB1*09:01 (OR=2.60, 95% CI 2.02-3.35, Pc=6.55×10(-13)) was associated with GD risk, while DRB1*12:02 (OR=0.32, 95% CI 0.20-0.53, Pc=4.55×10(-5)) was protective against GD. Transmission/disequilibrium test further confirmed an overtransmission of the DRB1*09:01 (OR 3.37, 95% CI 2.13-6.22, Pc=1.0×10(-5)) and an undertransmission of the DRB1*12:02 (OR 0.21, 95% CI 0.05-0.42, Pc=1.7×10(-3)). The findings were similar in females when stratified by gender. In conclusion, our results clearly identify that HLA-DRB1*09:01 confers susceptibility to GD and DRB1*12:02 exerts protection against GD development in Taiwanese children.
Department of Pediatrics, Mackay Memorial Hospital, and College of Medicine, Taipei Medical University, Taipei, Taiwan.
Y-L
YL
Wu
T-Y
TY
Chang
C-C
CC
Chu
C-Y
CY
Huang
F-S
FS
Lo
W-H
WH
Ting
C-H
CH
Lin
M
M
Lin
P-C
PC
Chiu
C-L
CL
Lin
W-F
WF
Chen
Y-J
YJ
Lee
D000293:Adolescent; D000483:Alleles; D000596:Amino Acids / Q000235:genetics; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005190:Family; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006111:Graves Disease / Q000235:genetics* / Q000276:immunology*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D035781:Siblings; D013624:Taiwan / Q000208:ethnology; D055815:Young Adult
D000596:Amino Acids; D059811:HLA-DRB1 Chains