Lack of association between autonomously functioning thyroid nodules and germline polymorphisms of the thyrotropin receptor and Gαs genes in a mild to moderate iodine-deficient Caucasian population

J Endocrinol Invest. 2014 Jul;37(7):625-30. doi: 10.1007/s40618-014-0081-x. Epub 2014 May 1.

Abstract

Background: Mutations of the thyrotropin receptor (TSHR) and/or Gαs gene have been found in a number of, but not all, autonomously functioning thyroid nodules (AFTNs). Recently, in a 15-year-old girl with a hyperfunctioning papillary thyroid carcinoma, we found two somatic and germline single nucleotide polymorphisms (SNPs): a SNP of the TSHR gene (exon 7, codon 187) and a SNP of Gαs gene (exon 8, codon 185). The same silent SNP of the TSHR gene had been reported in patients with AFTN or familial non-autoimmune hyperthyroidism. No further data about the prevalence of the two SNPs in AFTNs as well as in the general population are available in the literature.

Aim: To clarify the possible role of these SNPs in predisposing to AFTN.

Methods: Germline DNA was extracted from blood leukocytes of 115 patients with AFTNs (43 males and 72 females, aged 31-85 years, mean ± SD = 64 ± 13) and 100 sex-matched healthy individuals from the same geographic area, which is marginally iodine deficient. The genotype distribution of the two SNPs was investigated by restriction fragment length polymorphism-polymerase chain reaction.

Results: The prevalence of the two SNPs in our study population was low and not different to that found in healthy individuals: 8 % of patients vs. 9 % of controls were heterozygous for the TSHR SNP and 4 % patients vs. 6 % controls were heterozygous for the Gαs SNP. One patient harbored both SNPs.

Conclusions: These results suggest that these two SNPs do not confer susceptibility for the development of AFTN.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Alleles
  • Female
  • GTP-Binding Protein alpha Subunits, Gs / genetics*
  • Gene Frequency
  • Genetic Association Studies
  • Germ-Line Mutation*
  • Humans
  • Iodine / deficiency*
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Receptors, Thyrotropin / genetics*
  • Signal Transduction / genetics
  • Thyroid Nodule / genetics*
  • Thyroid Nodule / pathology
  • White People / genetics
  • Young Adult

Substances

  • Receptors, Thyrotropin
  • Iodine
  • GTP-Binding Protein alpha Subunits, Gs