Journal Article

Association of Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA4) Gene Polymorphisms with Autoimmune Thyroid Disease in Children and Adults: Case-Control Study

Lo, Fu-Sung, Huang, Chi-Yu, Cheng, Bi-Wen, Wang, Chao-Hung, Ting, Wei-Hsin, Chen, Chia-Ching, Chien, Ming-Nan, Chang, Tzu-Yang, Yang, Horng-Woei, Hung, Chen-Mei, Lin, Wen-Shan, Chan, Chon-In, Lin, Chao-Hsu, Wu, Yi-Lei, Li, Hsin-Jung, Lien, Ya-Ping, Lin, Chiung-Ling, Chen, Wei-Fang, Lee, Yann-Jinn

2016

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adolescent / Adult / Adults / Aged / Alleles / Antigens / Asian Continental Ancestry Group / Biology and Life Sciences / Case-Control Studies / Child / Child, Preschool / Children / Community colleges / Confidence intervals / CTLA-4 Antigen - genetics / CTLA-4 Antigen - immunology / CTLA-4 protein / Cytotoxicity / Disease control / Endocrinology / Female / Gene Expression / Gene Frequency / Gene polymorphism / Genes / Genetic aspects / Genetic polymorphisms / Genetic Predisposition to Disease / Genotypes / Graves Disease - ethnology / Graves Disease - genetics / Graves Disease - immunology / Graves Disease - pathology / Haplotypes / Hashimoto Disease - ethnology / Hashimoto Disease - genetics / Hashimoto Disease - immunology / Hashimoto Disease - pathology / Heterozygote / Hospitals / Humans / Linkage Disequilibrium / Lymphocytes / Lymphocytes T / Male / Medical research / Medicine / Medicine and Health Sciences / Metabolism / Middle Aged / Odds Ratio / Pathogenesis / Patients / Pediatrics / Physicians / Polymorphism / Polymorphism, Single Nucleotide / Proteins / Risk factors / Single-nucleotide polymorphism / T cell receptors / T cells / T-Lymphocytes, Cytotoxic - immunology / T-Lymphocytes, Cytotoxic - pathology / Thyroid / Thyroid diseases