Association of Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA4) Gene Polymorphisms with Autoimmune Thyroid Disease in Children and Adults: Case-Control Study.
Autoimmune thyroid disease (AITD), including Graves disease (GD) and Hashimoto disease (HD), is an organ-specific autoimmune disease with a strong genetic component. Although the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) polymorphism has been reported to be associated with AITD in adults, few studies have focused on children. The aim of our study was to investigate whether the CTLA4 polymorphisms, including -318C/T (rs5742909), +49A/G (rs231775), and CT60 (rs3087243), were associated with GD and HD in Han Chinese adults and children. We studied 289 adult GD, 265 pediatric GD, 229 pediatric HD patients, and 1058 healthy controls and then compared genotype, allele, carrier, and haplotype frequencies between patients and controls. We found that CTLA4 SNPs +49A/G and CT60 were associated with GD in adults and children. Allele G of +49A/G was significantly associated with GD in adults (odds ratio [OR], 1.50; 95% confidence interval [CI], 1.21-1.84; corrected P value [Pc] < 0.001) and children (OR, 1.42; 95% CI, 1.15-1.77; Pc = 0.002). Allele G of CT60 also significantly increased risk of GD in adults (OR, 1.63; 95% CI, 1.27-2.09; Pc < 0.001) and GD in children (OR, 1.58; 95% CI, 1.22-2.04; Pc < 0.001). Significant linkage disequilibrium was found between +49A/G and CT60 in GD and control subjects (D' = 0.92). Our results showed that CTLA4 was associated with both GD and HD and played an equivalent role in both adult and pediatric GD in Han Chinese population.
Department of Pediatrics, MacKay Children's Hospital, Taipei, Taiwan.|Department of Medicine, MacKay Medical College, New Taipei City, Taiwan.|MacKay Junior College of Medicine, Nursing and Management, New Taipei City, Taiwan.
Wei-Hsin
WH
Ting
Department of Endocrinology and Metabolism, MacKay Memorial Hospital, Taipei, Taiwan.|Department of Medicine, MacKay Medical College, New Taipei City, Taiwan.|Institute of Mechatronic Engineering, National Taipei University of Technology, Taipei, Taiwan.|MacKay Junior College of Medicine, Nursing and Management, New Taipei City, Taiwan.
Ming-Nan
MN
Chien
Department of Pediatrics, Chang Gung Memorial Hospital, Tao-Yuan, Taiwan.|College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
Fu-Sung
FS
Lo
Department of Endocrinology and Metabolism, MacKay Memorial Hospital, Taipei, Taiwan.
Chao-Hung
CH
Wang
Department of Pediatrics, MacKay Children's Hospital, Taipei, Taiwan.|Department of Medicine, MacKay Medical College, New Taipei City, Taiwan.
Chi-Yu
CY
Huang
Department of Medical Research, MacKay Memorial Hospital Tamsui, New Taipei City, Taiwan.
Chiung-Ling
CL
Lin
Department of Medical Research, MacKay Memorial Hospital Tamsui, New Taipei City, Taiwan.
Wen-Shan
WS
Lin
Department of Medical Research, MacKay Memorial Hospital Tamsui, New Taipei City, Taiwan.
Tzu-Yang
TY
Chang
Department of Medical Research, MacKay Memorial Hospital Tamsui, New Taipei City, Taiwan.
Horng-Woei
HW
Yang
Department of Medical Research, MacKay Memorial Hospital Tamsui, New Taipei City, Taiwan.
Wei-Fang
WF
Chen
Department of Medical Research, MacKay Memorial Hospital Tamsui, New Taipei City, Taiwan.
Ya-Ping
YP
Lien
Department of Pediatrics, MacKay Memorial Hospital HsinChu, Hsin-Chu, Taiwan.
Bi-Wen
BW
Cheng
Department of Pediatrics, MacKay Memorial Hospital HsinChu, Hsin-Chu, Taiwan.
Chao-Hsu
CH
Lin
Department of Pediatrics, Chiayi Christian Hospital, Chia-Yi, Taiwan.
Chia-Ching
CC
Chen
Department of Pediatrics, Changhua Christian Hospital, Chang-Hua, Taiwan.
Yi-Lei
YL
Wu
Department of Pediatrics, Hsinchu Cathay General Hospital, Hsin-Chu, Taiwan.
Chen-Mei
CM
Hung
Department of Pediatrics, St. Martin De Porres Hospital, Chia-Yi, Taiwan.
Hsin-Jung
HJ
Li
Department of Pediatrics, MacKay Children's Hospital, Taipei, Taiwan.
Chon-In
CI
Chan
Department of Pediatrics, MacKay Children's Hospital, Taipei, Taiwan.|Department of Medicine, MacKay Medical College, New Taipei City, Taiwan.|Department of Medical Research, MacKay Memorial Hospital Tamsui, New Taipei City, Taiwan.|Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Institute of Biomedical Sciences, MacKay Medical College, New Taipei City, Taiwan.
Yann-Jinn
YJ
Lee
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People; D060908:CTLA-4 Antigen / Q000235:genetics* / Q000276:immunology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006111:Graves Disease / Q000208:ethnology / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D006239:Haplotypes; D050031:Hashimoto Disease / Q000208:ethnology / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D006579:Heterozygote; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology
D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human