RAGE polymorphisms and oxidative stress levels in Hashimoto's thyroiditis

Eur J Clin Invest. 2017 May;47(5):341-347. doi: 10.1111/eci.12739. Epub 2017 Mar 20.

Abstract

Background: Polymorphisms of the receptor for advanced glycation end products (RAGE) gene have been studied in various autoimmune disorders, but not in Hashimoto's thyroiditis. Also, increased oxidative stress has been described in patients with Hashimoto's thyroiditis. The aim of this study was to investigate the possible role of two common RAGE polymorphisms (-429T>C, -374T>A) in Hashimoto's thyroiditis; in parallel, we studied oxidative stress levels.

Materials and methods: A total of 300 consecutive euthyroid women were examined and classified into three groups: Hashimoto's thyroiditis with treatment (n = 96), Hashimoto's thyroiditis without treatment (n = 109) and controls (n = 95). For a rough evaluation of oxidative stress, total lipid peroxide levels in serum were measured. The -429T>C AluI and -374T>A MfeI polymorphisms of RAGE were studied in genomic DNA.

Results: Significant association of the RAGE system with Hashimoto's thyroiditis was found only with regard to the prevalence of the -429T>C, but not with -374T>A polymorphism. The levels of oxidative stress were significantly elevated in Hashimoto's thyroiditis patients under treatment. Further analysis demonstrated that an oxidative stress cut-off value of 590 μmol/L is associated with an increased risk of progression of Hashimoto's thyroiditis from euthyroidism to hypothyroidism; this risk is further increased in carriers of the RAGE -429T>C polymorphism.

Conclusions: Our findings indicate that both examined risk factors may be implicated in the occurrence of Hashimoto's thyroiditis, but this covers only a fraction of the pathophysiology of the disease.

Keywords: Autoimmune disease; Hashimoto's thyroiditis; RAGE gene polymorphisms; oxidative stress.

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / genetics*
  • Case-Control Studies
  • Cross-Sectional Studies
  • Female
  • Genetic Predisposition to Disease
  • Greece
  • Hashimoto Disease / genetics*
  • Hashimoto Disease / metabolism
  • Humans
  • Lipid Peroxides / metabolism
  • Middle Aged
  • Mitogen-Activated Protein Kinases / genetics*
  • Oxidative Stress*
  • Polymorphism, Genetic
  • Young Adult

Substances

  • Antigens, Neoplasm
  • Lipid Peroxides
  • MOK protein, human
  • Mitogen-Activated Protein Kinases