Association of functional GITR gene polymorphisms related to expression of glucocorticoid-induced tumour necrosis factor-receptor (GITR) molecules with prognosis of autoimmune thyroid disease

Clin Exp Immunol. 2011 Aug;165(2):141-7. doi: 10.1111/j.1365-2249.2011.04414.x. Epub 2011 May 19.

Abstract

The glucocorticoid-induced tumour necrosis factor (TNF)-receptor (GITR) affects the functions of regulatory T (T(reg)) and effector T (T(eff)) cells, but the significance of this phenomenon is still unclear. To examine the association of single nucleotide polymorphisms (SNPs) in the GITR gene with the expression of GITR molecules on T cells and with the pathological conditions in patients with autoimmune thyroid disease (AITD), we examined the frequencies of four candidate SNPs in AITD patients and healthy volunteers by restriction enzyme analysis and direct sequence analyses. We also analysed the GITR expression on peripheral T(reg) and T(eff) cells in AITD patients by three-colour flow cytometry. The CC genotype in the rs3753348 C/G SNP was significantly more frequent in patients with mild Hashimoto's disease (HD) than in those with severe HD [P = 0·0117, odds ratio (OR) = 3·13]. The AA genotype in the rs2298213 A/G SNP was significantly more frequent in patients with mild HD than in patients with severe HD (P = 0·010, OR = 4·43). All patients and healthy individuals had the GG genotype in rs60038293 A/G and rs11466696 A/G SNPs. The proportions of GITR(+) cells in T(reg) and T(eff) cells were significantly higher in AITD patients with the CC genotype of the rs3753348 SNP than in those with the GG genotype (P = 0·004 and P = 0·011, respectively). In conclusion, the rs3753348 C/G SNP in the GITR is associated with HD prognosis and expression on T(reg) and T(eff) cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Base Sequence
  • Female
  • Flow Cytometry
  • Gene Frequency
  • Genotype
  • Glucocorticoid-Induced TNFR-Related Protein / biosynthesis
  • Glucocorticoid-Induced TNFR-Related Protein / genetics*
  • Graves Disease / genetics*
  • Graves Disease / immunology
  • Hashimoto Disease / diagnosis
  • Hashimoto Disease / genetics*
  • Hashimoto Disease / immunology
  • Humans
  • Male
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / genetics
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Restriction Mapping
  • Sequence Analysis, DNA
  • T-Lymphocyte Subsets / metabolism*
  • T-Lymphocytes, Regulatory / metabolism*
  • T-Lymphocytes, Regulatory / pathology

Substances

  • Glucocorticoid-Induced TNFR-Related Protein
  • Membrane Proteins
  • TNFRSF18 protein, human