Artículo de revista
Haplotype Analysis of the Promoter Region of Phosphodiesterase Type 8B (PDE8B) in Correlation with Inactivating PDE8B Mutation and the Serum Thyroid-Stimulating Hormone Levels
Fecha
2010Registro en:
THYROID, Volume 20, Number 4, 2010
DOI: 10.1089=thy.2009.0260
Autor
Horvath, Anelia
Faucz, Fabio
Finkielstain, Gabriela P.
Nikita, Maria Eleni
Rothenbuhler, Anya
Almeida, Madson
Mericq, Verónica
Stratakis, Constantine A.
Institución
Resumen
Background: Human phosphodiesterase (PDE) type 8B (PDE8B) is located at 5q14.1 and is known as the PDE
with the highest affinity to cAMP. We recently described a family with bilateral micronodular adrenocortical
disease that was apparently caused by an inactivating PDE8B mutation (H305P). As a result of a genome-wide
study, a strong association between six polymorphic variants in the PDE8B promoter and serum levels of the
thyroid-stimulating hormone (TSH) has been recently reported. Despite an extended analysis of the regions
surrounding 5q14.1, no other potential genetic variants that could be responsible for the associated TSH levels
were found.
Methods: In this study, we genotyped by polymerase chain reaction the described six polymorphic variants in
the PDE8B promoter in the family with micronodular adrenocortical disease and inactivating PDE8B mutation
and analyzed their correlation with individual TSH values in the family members.
Results: We observed complete segregation between the reported association and individual TSH values in the
family we studied. Haplotype analysis showed that the haplotype associated with the high TSH levels is different
from the one that segregated with H305P, suggesting that the mutation most probably has arisen on an
allele independent of the high TSH-associated allele.
Conclusions: The proposed mechanism by which PDE8B may influence TSH levels is through control of cAMP
signaling. Our analysis revealed separate segregation of an inactivating PDE8B allele from the high-TSH-allele
and showed low TSH levels in persons who carry an inactivating PDE8B allele. These data suggest that, indeed,
PDE8B may be involved in regulation of TSH levels.