Endocrine Abstracts (2012) 29 P1611

Frequency of PDE8B gene polymorphisms in patients affected by sporadic and familiar nonautoimmune subclinical hypothyroidism

P. Agretti, E. Ferrarini, G. De Marco, A. Dimida, A. Molinaro, F. Niccolai, A. Pinchera, P. Vitti & M. Tonacchera


University of Pisa, Pisa, Italy.


Background: Nonautoimmune subclinical hypothyroidism is characterized by elevated serum levels of TSH in the presence of normal thyroid hormone levels and absence of anti-thyroid antibodies. As a result of a genomic-wide study, a strong association between three polymorphic variants in exon 1 of human phosphodiesterase 8B (PDE8B) gene (rs4704397, rs6885099 e rs2046045) and serum levels of TSH has been recently reported. The aim of the present study was to evaluate the frequency of PDE8B gene polymorphisms in a group of patients affected by sporadic or familial nonautoimmune subclinical hypothyroidism.

Methods: The study group comprised 113 patients affected by sporadic (101) or familial (12) nonautoimmune subclinical hypothyroidism with elevated serum TSH levels (medium serum TSH 8.997±12.48 μU/ml) and normal free circulating T3 (FT3) and T4 (FT4) levels. Genomic DNA was obtained from whole blood of patients using standard procedures to genotype patients for specific single nucleotide polymorphism (SNP) of PDE8B gene by TaqMan SNP genotyping assay and to sequence the entire coding region of the TSH receptor (TSHr) gene.

Results: The ancestral allele associated with increased TSH level was present in 82/113 patients (73%) for rs4704397, in 79/113 patients (70%) for rs6885099 and in 84/113 patients (74%) for rs2046045. However, similar values of serum TSH were detected in patients with minor or major allele for each polymorphism. Genetic analysis revealed the presence of TSHr gene mutations at the heterozygous state (D36H, P52T polymorphic variants; P68S, R109Q and P162A mild inactivating mutations) in 17/113 patients.

Conclusion: A prevalence of the minor allele of PDE8B gene SNPs associated with elevated serum levels of TSH was demonstrated in patients affected by sporadic or familial nonautoimmune subclinical hypothyroidism, 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 circulating TSH levels in these patients.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

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