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.
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.


OBJECTIVE
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.
Department of Clinical and Experimental Medicine, Unit of Endocrinology, Policlinico "G. Martino", Messina, Italy.
Teresa Manuela
TM
Vicchio
Salvatore
S
Giovinazzo
Rosaria
R
Certo
Mariapaola
M
Cucinotta
Carmelo
C
Micali
Sergio
S
Baldari
Salvatore
S
Benvenga
Francesco
F
Trimarchi
Alfredo
A
Campennì
Rosaria Maddalena
RM
Ruggeri
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D005787:Gene Frequency; D056726:Genetic Association Studies; D018095:Germ-Line Mutation; D006801:Humans; D007455:Iodine / Q000172:deficiency*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011989:Receptors, Thyrotropin / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D016606:Thyroid Nodule / Q000235:genetics* / Q000473:pathology; D044465:White People / Q000235:genetics; D055815:Young Adult
D011989:Receptors, Thyrotropin; D007455:Iodine; D019205:GTP-Binding Protein alpha Subunits, Gs