OBJECTIVE: Variation in thyroid hormone (TH) concentrations between subjects is greater than in a single subject over a prolonged period of time, suggesting an individual set point for thyroid function. We have previously shown that TH levels within normal range are associated with clinical indices such as bone mass, BMI, and heart rate. The aim of this study on young men was therefore to gain insight into the determinants of variation in TH levels among healthy subjects. METHODS: Healthy male siblings (n=941, 25-45 years) were recruited in a cross-sectional, population-based study; a history or treatment of thyroid disease and thyroid auto-immunity were exclusion criteria. A complete assessment of TH status was performed (TSH, free thyroxine (FT4), free triiodothyronine (FT3), thyroperoxidase, and thyroglobulin antibodies, reverse T3 (rT3), thyroid-binding globulin (TBG), and urinary iodine levels). Genotyping was performed by TaqMan and KASP (KBiosciences) genotyping assays. RESULTS: (F)T4, rT3, and TBG had heritability estimates between 80 and 90%. Estimates were lower for (F)T3 (60%) and lowest for TSH (49%). Significant associations were observed between different single-nucleotide polymorphisms (SNPs) in the thyroid pathway and TSH, FT4, ratio FT3:FT4, and rT3. Nevertheless, these SNPs only explain a limited part of the heredity. As to age and lifestyle-related factors, (F)T3 was negatively related to age and education level, positively to smoking and BMI (all P<0.0001) but not substantially to urinary iodine concentrations. Smoking was also negatively related to TSH and positively to FT4. CONCLUSION: Both genetic and lifestyle-related factors play a role in determining between-subject variation in TH levels in euthyroid young men, although genetic factors seem most important.
OBJECTIVE: Variation in thyroid hormone (TH) concentrations between subjects is greater than in a single subject over a prolonged period of time, suggesting an individual set point for thyroid function. We have previously shown that TH levels within normal range are associated with clinical indices such as bone mass, BMI, and heart rate. The aim of this study on young men was therefore to gain insight into the determinants of variation in TH levels among healthy subjects. METHODS: Healthy male siblings (n=941, 25-45 years) were recruited in a cross-sectional, population-based study; a history or treatment of thyroid disease and thyroid auto-immunity were exclusion criteria. A complete assessment of TH status was performed (TSH, free thyroxine (FT4), free triiodothyronine (FT3), thyroperoxidase, and thyroglobulin antibodies, reverse T3 (rT3), thyroid-binding globulin (TBG), and urinary iodine levels). Genotyping was performed by TaqMan and KASP (KBiosciences) genotyping assays. RESULTS: (F)T4, rT3, and TBG had heritability estimates between 80 and 90%. Estimates were lower for (F)T3 (60%) and lowest for TSH (49%). Significant associations were observed between different single-nucleotide polymorphisms (SNPs) in the thyroid pathway and TSH, FT4, ratio FT3:FT4, and rT3. Nevertheless, these SNPs only explain a limited part of the heredity. As to age and lifestyle-related factors, (F)T3 was negatively related to age and education level, positively to smoking and BMI (all P<0.0001) but not substantially to urinary iodine concentrations. Smoking was also negatively related to TSH and positively to FT4. CONCLUSION: Both genetic and lifestyle-related factors play a role in determining between-subject variation in TH levels in euthyroid young men, although genetic factors seem most important.
Authors: Johannes W Dietrich; Patrick Müller; Fabian Schiedat; Markus Schlömicher; Justus Strauch; Apostolos Chatzitomaris; Harald H Klein; Andreas Mügge; Josef Köhrle; Eddy Rijntjes; Ina Lehmphul Journal: Eur Thyroid J Date: 2015-05-23
Authors: Thomas G Travison; Hubert W Vesper; Eric Orwoll; Frederick Wu; Jean Marc Kaufman; Ying Wang; Bruno Lapauw; Tom Fiers; Alvin M Matsumoto; Shalender Bhasin Journal: J Clin Endocrinol Metab Date: 2017-04-01 Impact factor: 5.958
Authors: Eleanor M Simonsick; Chee W Chia; Jennifer S Mammen; Josephine M Egan; Luigi Ferrucci Journal: J Gerontol A Biol Sci Med Sci Date: 2016-01-20 Impact factor: 6.053
Authors: Alexander Teumer; Layal Chaker; Stefan Groeneweg; Yong Li; Celia Di Munno; Caterina Barbieri; Ulla T Schultheiss; Michela Traglia; Tarunveer S Ahluwalia; Masato Akiyama; Emil Vincent R Appel; Dan E Arking; Alice Arnold; Arne Astrup; Marian Beekman; John P Beilby; Sofie Bekaert; Eric Boerwinkle; Suzanne J Brown; Marc De Buyzere; Purdey J Campbell; Graziano Ceresini; Charlotte Cerqueira; Francesco Cucca; Ian J Deary; Joris Deelen; Kai-Uwe Eckardt; Arif B Ekici; Johan G Eriksson; Luigi Ferrrucci; Tom Fiers; Edoardo Fiorillo; Ian Ford; Caroline S Fox; Christian Fuchsberger; Tessel E Galesloot; Christian Gieger; Martin Gögele; Alessandro De Grandi; Niels Grarup; Karin Halina Greiser; Kadri Haljas; Torben Hansen; Sarah E Harris; Diana van Heemst; Martin den Heijer; Andrew A Hicks; Wouter den Hollander; Georg Homuth; Jennie Hui; M Arfan Ikram; Till Ittermann; Richard A Jensen; Jiaojiao Jing; J Wouter Jukema; Eero Kajantie; Yoichiro Kamatani; Elisa Kasbohm; Jean-Marc Kaufman; Lambertus A Kiemeney; Margreet Kloppenburg; Florian Kronenberg; Michiaki Kubo; Jari Lahti; Bruno Lapauw; Shuo Li; David C M Liewald; Ee Mun Lim; Allan Linneberg; Michela Marina; Deborah Mascalzoni; Koichi Matsuda; Daniel Medenwald; Christa Meisinger; Ingrid Meulenbelt; Tim De Meyer; Henriette E Meyer Zu Schwabedissen; Rafael Mikolajczyk; Matthijs Moed; Romana T Netea-Maier; Ilja M Nolte; Yukinori Okada; Mauro Pala; Cristian Pattaro; Oluf Pedersen; Astrid Petersmann; Eleonora Porcu; Iris Postmus; Peter P Pramstaller; Bruce M Psaty; Yolande F M Ramos; Rajesh Rawal; Paul Redmond; J Brent Richards; Ernst R Rietzschel; Fernando Rivadeneira; Greet Roef; Jerome I Rotter; Cinzia F Sala; David Schlessinger; Elizabeth Selvin; P Eline Slagboom; Nicole Soranzo; Thorkild I A Sørensen; Timothy D Spector; John M Starr; David J Stott; Youri Taes; Daniel Taliun; Toshiko Tanaka; Betina Thuesen; Daniel Tiller; Daniela Toniolo; Andre G Uitterlinden; W Edward Visser; John P Walsh; Scott G Wilson; Bruce H R Wolffenbuttel; Qiong Yang; Hou-Feng Zheng; Anne Cappola; Robin P Peeters; Silvia Naitza; Henry Völzke; Serena Sanna; Anna Köttgen; Theo J Visser; Marco Medici Journal: Nat Commun Date: 2018-10-26 Impact factor: 14.919