Phosphodiesterase 8B Gene Variants Are Associated with Serum TSH Levels and Thyroid Function. (Articolo in rivista)

Type
Label
  • Phosphodiesterase 8B Gene Variants Are Associated with Serum TSH Levels and Thyroid Function. (Articolo in rivista) (literal)
Anno
  • 2008-01-01T00:00:00+01:00 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
  • 10.1016/j.ajhg.2008.04.019 (literal)
Alternative label
  • Lisette Arnaud-Lopez,1,11; Gianluca Usala,2,11; Graziano Ceresini,3; Braxton D. Mitchell,4; Maria Grazia Pilia,2; Maria Grazia Piras,2; Natascia Sestu,2; Andrea Maschio,2; Fabio Busonero,2; Giuseppe Albai,2; Mariano Dei,2; Sandra Lai,2; Antonella Mulas,2; Laura Crisponi,2; Toshiko Tanaka,5; Stefania Bandinelli,6; Jack M. Guralnik,7; Angela Loi,2; Lenuta Balaci,2; Gabriella Sole,2; Alessia Prinzis,8; Stefano Mariotti,8; Alan R. Shuldiner,4,9; Antonio Cao,2; David Schlessinger,1; Manuela Uda,2; Gonçalo R. Abecasis,10; Ramaiah Nagaraja,1; Serena Sanna,2; and Silvia Naitza2 (2008)
    Phosphodiesterase 8B Gene Variants Are Associated with Serum TSH Levels and Thyroid Function.
    in American journal of human genetics
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Lisette Arnaud-Lopez,1,11; Gianluca Usala,2,11; Graziano Ceresini,3; Braxton D. Mitchell,4; Maria Grazia Pilia,2; Maria Grazia Piras,2; Natascia Sestu,2; Andrea Maschio,2; Fabio Busonero,2; Giuseppe Albai,2; Mariano Dei,2; Sandra Lai,2; Antonella Mulas,2; Laura Crisponi,2; Toshiko Tanaka,5; Stefania Bandinelli,6; Jack M. Guralnik,7; Angela Loi,2; Lenuta Balaci,2; Gabriella Sole,2; Alessia Prinzis,8; Stefano Mariotti,8; Alan R. Shuldiner,4,9; Antonio Cao,2; David Schlessinger,1; Manuela Uda,2; Gonçalo R. Abecasis,10; Ramaiah Nagaraja,1; Serena Sanna,2; and Silvia Naitza2 (literal)
Pagina inizio
  • 1270 (literal)
Pagina fine
  • 1280 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 82 (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • 1Laboratory of Genetics, National Institute on Aging, Baltimore, MD 21224, USA 2Istituto di Neurogenetica e Neurofarmacologia, Consiglio Nazionale delle Ricerche, 09042 Cagliari, Italy 3Department of Internal Medicine, Section of Geriatrics, University of Parma, 43100 Parma, Italy 4Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA 5Clinical Research Branch, National Institute on Aging, Baltimore, MD 21225, USA 6Geriatric Rehabilitation Unit, Azienda Sanitaria Firenze (ASF), 50125 Florence, Italy 7Laboratory of Epidemiology, Demography and Biometry, National Institute on Aging, Bethesda, MD 20892, USA 8Endocrinology, Department of Medical Sciences \"M. Aresu,\" University of Cagliari, 09042 Cagliari, Italy 9Geriatric Research and Education Clinical Center, Veterans Administration Medical Center, Baltimore, MD 21201, USA 10Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA (literal)
Titolo
  • Phosphodiesterase 8B Gene Variants Are Associated with Serum TSH Levels and Thyroid Function. (literal)
Abstract
  • Thyroid-stimulating hormone (TSH) controls thyroid growth and hormone secretion through binding to its G protein-coupled receptor (TSHR) and production of cyclic AMP (cAMP). Serum TSH is a sensitive indicator of thyroid function, and overt abnormalities in thyroid function lead to common endocrine disorders affecting ~10% of individuals over a life span. By genotyping 362,129 SNPs in 4,300 Sardinians, we identified a strong association (p = 1.3 × 10-11) between alleles of rs4704397 and circulating TSH levels; each additional copy of the minor A allele was associated with an increase of 0.13 ?IU/ml in TSH. The single-nucleotide polymorphism (SNP) is located in intron 1 of PDE8B, encoding a high-affinity cAMP-specific phosphodiesterase. The association was replicated in 4,158 individuals, including additional Sardinians and two genetically distant cohorts from Tuscany and the Old Order Amish (overall p value = 1.9 × 10-20). In addition to association of TSH levels with SNPs in PDE8B, our genome scan provided evidence for association with PDE10A and several biologically interesting candidates in a focused analysis of 24 genes. In particular, we found evidence for association of TSH levels with SNPs in the THRB (rs1505287, p = 7.3 × 10-5), GNAQ (rs10512065, p = 2.0 × 10-4), TG (rs2252696, p = 2.2 × 10-3), POU1F1 (rs1976324, p = 3.9 × 10-3), PDE4D (rs27178, p = 8.3 × 10-3), and TSHR (rs4903957, p = 8.6 × 10-3) loci. Overall, the results suggest a primary effect of PDE8B variants on cAMP levels in the thyroid. This would affect production of T4 and T3 and feedback to alter TSH release by the pituitary. PDE8B may thus provide a candidate target for the treatment of thyroid dysfunction. (literal)
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