BACKGROUND: Maternal subclinical hypothyroidism is associated with a number of adverse outcomes in pregnancy. The Endocrine Society's recent consensus guidelines have recommended treatment with T(4) for this condition in pregnancy. The single nucleotide polymorphism rs4704397 in the phosphodiesterase 8B (PDE8B) gene has been found to be associated with altered serum TSH concentrations in the general population. We aimed to assess whether genetic variation in TSH due to the rs4704397 genotype affects the number of individuals classified as having subclinical hypothyroidism in pregnancy. METHODS: Serum TSH, FT4, FT3, and thyroid peroxidase antibodies (TPOAbs) were measured in 970 pregnant women at 28 wk gestation. rs4704397 genotype was available on 877 subjects. Reference range calculations were based on the TPOAb-negative women. RESULTS: TSH, but not FT4, FT3, or TPOAbs, varied with genotype and was highest in those with the AA genotype (median, 2.16, 1.84, and 1.73 mIU/liter for AA, AG, and GG genotypes, respectively; P = 0.0004). A greater proportion of women with the AA genotype had TSH concentrations above 4.21 mIU/liter, the upper limit of the reference range, compared with the AG and GG genotypes (9.6 vs. 3.5%, respectively; P = 0.004). Maternal PDE8B genotype was not associated with offspring birthweight or gestational age at delivery. CONCLUSION: Genetic variation in TSH levels in pregnancy associated with the PDE8B rs4704397 genotype has implications for the number of women treated for subclinical hypothyroidism under current guidelines. Consideration should be made to individualization of normal ranges, potential effects on pregnancy outcome, and intention to treat for subclinical hypothyroidism in pregnancy.
BACKGROUND: Maternal subclinical hypothyroidism is associated with a number of adverse outcomes in pregnancy. The Endocrine Society's recent consensus guidelines have recommended treatment with T(4) for this condition in pregnancy. The single nucleotide polymorphism rs4704397 in the phosphodiesterase 8B (PDE8B) gene has been found to be associated with altered serum TSH concentrations in the general population. We aimed to assess whether genetic variation in TSH due to the rs4704397 genotype affects the number of individuals classified as having subclinical hypothyroidism in pregnancy. METHODS: Serum TSH, FT4, FT3, and thyroid peroxidase antibodies (TPOAbs) were measured in 970 pregnant women at 28 wk gestation. rs4704397 genotype was available on 877 subjects. Reference range calculations were based on the TPOAb-negative women. RESULTS:TSH, but not FT4, FT3, or TPOAbs, varied with genotype and was highest in those with the AA genotype (median, 2.16, 1.84, and 1.73 mIU/liter for AA, AG, and GG genotypes, respectively; P = 0.0004). A greater proportion of women with the AA genotype had TSH concentrations above 4.21 mIU/liter, the upper limit of the reference range, compared with the AG and GG genotypes (9.6 vs. 3.5%, respectively; P = 0.004). Maternal PDE8B genotype was not associated with offspring birthweight or gestational age at delivery. CONCLUSION: Genetic variation in TSH levels in pregnancy associated with the PDE8Brs4704397 genotype has implications for the number of women treated for subclinical hypothyroidism under current guidelines. Consideration should be made to individualization of normal ranges, potential effects on pregnancy outcome, and intention to treat for subclinical hypothyroidism in pregnancy.
Authors: Ana M Peiró; Chih-Min Tang; Fiona Murray; Lingzhi Zhang; Loren M Brown; Daisy Chou; Laura Rassenti; Thomas J Kipps; Thomas A Kipps; Paul A Insel Journal: J Hum Genet Date: 2011-07-28 Impact factor: 3.172
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Authors: P Agretti; G De Marco; C Di Cosmo; B Bagattini; E Ferrarini; L Montanelli; P Vitti; M Tonacchera Journal: J Endocrinol Invest Date: 2014-01-09 Impact factor: 4.256
Authors: Peter N Taylor; Vijay Panicker; Adrian Sayers; Beverley Shields; Ahmed Iqbal; Alexandra P Bremner; John P Beilby; Peter J Leedman; Andrew T Hattersley; Bijay Vaidya; Timothy Frayling; Jonathan Evans; Jonathan H Tobias; Nicholas J Timpson; John P Walsh; Colin M Dayan Journal: Eur J Endocrinol Date: 2011-02-11 Impact factor: 6.664
Authors: Eleonora Porcu; Marco Medici; Giorgio Pistis; Claudia B Volpato; Scott G Wilson; Anne R Cappola; Steffan D Bos; Joris Deelen; Martin den Heijer; Rachel M Freathy; Jari Lahti; Chunyu Liu; Lorna M Lopez; Ilja M Nolte; Jeffrey R O'Connell; Toshiko Tanaka; Stella Trompet; Alice Arnold; Stefania Bandinelli; Marian Beekman; Stefan Böhringer; Suzanne J Brown; Brendan M Buckley; Clara Camaschella; Anton J M de Craen; Gail Davies; Marieke C H de Visser; Ian Ford; Tom Forsen; Timothy M Frayling; Laura Fugazzola; Martin Gögele; Andrew T Hattersley; Ad R Hermus; Albert Hofman; Jeanine J Houwing-Duistermaat; Richard A Jensen; Eero Kajantie; Margreet Kloppenburg; Ee M Lim; Corrado Masciullo; Stefano Mariotti; Cosetta Minelli; Braxton D Mitchell; Ramaiah Nagaraja; Romana T Netea-Maier; Aarno Palotie; Luca Persani; Maria G Piras; Bruce M Psaty; Katri Räikkönen; J Brent Richards; Fernando Rivadeneira; Cinzia Sala; Mona M Sabra; Naveed Sattar; Beverley M Shields; Nicole Soranzo; John M Starr; David J Stott; Fred C G J Sweep; Gianluca Usala; Melanie M van der Klauw; Diana van Heemst; Alies van Mullem; Sita H Vermeulen; W Edward Visser; John P Walsh; Rudi G J Westendorp; Elisabeth Widen; Guangju Zhai; Francesco Cucca; Ian J Deary; Johan G Eriksson; Luigi Ferrucci; Caroline S Fox; J Wouter Jukema; Lambertus A Kiemeney; Peter P Pramstaller; David Schlessinger; Alan R Shuldiner; Eline P Slagboom; André G Uitterlinden; Bijay Vaidya; Theo J Visser; Bruce H R Wolffenbuttel; Ingrid Meulenbelt; Jerome I Rotter; Tim D Spector; Andrew A Hicks; Daniela Toniolo; Serena Sanna; Robin P Peeters; Silvia Naitza Journal: PLoS Genet Date: 2013-02-07 Impact factor: 5.917