Analysis of the genetic variability of the 1st (CCC/ACC, P52T) and the 10th exons (bp 1012-1704) of the TSH receptor gene in Graves' disease

Eur J Immunogenet. 2000 Feb;27(1):17-23. doi: 10.1046/j.1365-2370.2000.00187.x.


We determined the genetic variability of the 1st (CCC/ACC, P52T polymorphic variant) and 10th exons (bp 1012-1704) of the TSH receptor (TSHR) gene in Graves' disease. A total of 101 Graves' patients and 163 control subjects were screened. The A253 mutant allele was carried by nine patients with Graves' disease (8.91%) and 13 control subjects (7.98%) in heterozygous genotype. No significant difference in the frequency of the mutant allele was found between Graves' patients and control subjects. These results provide evidence that the A253 polymorphism has no genetic relevance in Graves' disease. Moreover, the DNA nucleotide sequence of 693 bp of the 10th exon (bp 1012-1704) of the TSHR gene was determined in 15 Graves' patients. Six patients were homozygous for the wild-type allele and nine were heterozygous for the mutant allele at the 253rd nucleotide of the first exon. No polymorphism was found in the DNA sequences obtained from leukocytes of Graves' patients, similarly to the sequences obtained from the nine control subjects. None of the nine patients carrying the A253 polymorphism in the 1st exon of the TSHR had polymorphism in the examined part of the 10th exon, including two additional patients whose thyroid tissue was directly analysed. In all likelihood, the polymorphisms of the examined regions of either the 1st or the 10th exon of the THSR gene do not contribute to the genetic susceptibility to Graves' disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Alleles
  • Amino Acid Sequence
  • Base Sequence
  • Case-Control Studies
  • Exons
  • Female
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Genotype
  • Graves Disease / genetics*
  • Graves Disease / immunology
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Polymorphism, Genetic
  • Receptors, Thyrotropin / genetics*


  • Receptors, Thyrotropin