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

PLoS One. 2016 Apr 25;11(4):e0154394. doi: 10.1371/journal.pone.0154394. eCollection 2016.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Asian People
  • CTLA-4 Antigen / genetics*
  • CTLA-4 Antigen / immunology
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Female
  • Gene Expression
  • Gene Frequency
  • Genetic Predisposition to Disease*
  • 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
  • Humans
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Odds Ratio
  • Polymorphism, Single Nucleotide*
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / pathology

Substances

  • CTLA-4 Antigen
  • CTLA4 protein, human

Grants and funding

This study was supported by grants NSC 101-2314-B-715-002-MY3 from the Ministry of Science and Technology, Executive Yuan; MMH E-102-07 from MacKay Memorial Hospital, Taipei; and MMC RD1010045 from MacKay Medical College, New Taipei City, Taiwan.