Frequency and effect on serum TSH of phosphodiesterase 8B (PDE8B) gene polymorphisms in patients with sporadic nonautoimmune subclinical hypothyroidism

Nonautoimmune subclinical hypothyroidism (NSH) is characterized by elevated serum TSH in presence of normal thyroid hormone levels and absence of anti-thyroid antibodies. As result of a genomic-wide study, a strong association between three polymorphic variants in intron 1 of human PDE8B gene (rs4704397, rs6885099, rs2046045) and serum TSH has been reported in euthyroid subjects.The aim of this study was to evaluate frequency and effects on serum TSH of PDE8B gene polymorphisms in patients with sporadic NSH and verify if differences in serum TSH levels are associated to these polymorphic variants.A total of 58 Italian selected patients affected by NSH, with elevated serum TSH, normal FT3 and FT4 and without TSHr gene mutations, were subjected to genotyping for specific single nucleotide polymorphism of PDE8B gene.In all patients, the integrity of TSH receptor gene was attested. The ancestral allele associated with increased serum TSH was present in 42/58 patients (72.4 %) for rs4704397, in 42/58 patients (72.4 %) for rs6885099 and in 44/58 patients (75.9 %) for rs2046045. However, similar values of serum TSH were detected in patients with minor or major allele for each polymorphism.A prevalence of the minor allele of PDE8B gene polymorphism associated with elevated serum levels of TSH was demonstrated in patients affected by sporadic NSH; however, significant differences in circulating TSH in patients with minor or major alleles for each polymorphism were not identified demonstrating the lack of association between the polymorphisms and serum TSH levels in these patients.