title: TSHR intronic polymorphisms (rs179247 and rs12885526) and their role in the susceptibility of the Brazilian population to Graves' disease and Graves' ophthalmopathy.
abstract: OBJECTIVE
  Intronic thyroid-stimulating hormone receptor polymorphisms have been associated with the risk for both Graves' disease and Graves' ophthalmopathy, but results have been inconsistent among different populations. We aimed to investigate the influence of thyroid-stimulating hormone receptor intronic polymorphisms in a large well-characterized population of GD patients.
  
  
  METHODS
  We studied 279 Graves' disease patients (231 females and 48 males, 39.80 ± 11.69 years old), including 144 with Graves' ophthalmopathy, matched to 296 healthy control individuals. Thyroid-stimulating hormone receptor genotypes of rs179247 and rs12885526 were determined by Real Time PCR TaqMan(®) SNP Genotyping.
  
  
  RESULTS
  A multivariate analysis showed that the inheritance of the thyroid-stimulating hormone receptor AA genotype for rs179247 increased the risk for Graves' disease (OR = 2.821; 95 % CI 1.595-4.990; p = 0.0004), whereas the thyroid-stimulating hormone receptor GG genotype for rs12885526 increased the risk for Graves' ophthalmopathy (OR = 2.940; 95 % CI 1.320-6.548; p = 0.0083). Individuals with Graves' ophthalmopathy also presented lower mean thyrotropin receptor antibodies levels (96.3 ± 143.9 U/L) than individuals without Graves' ophthalmopathy (98.3 ± 201.9 U/L). We did not find any association between the investigated polymorphisms and patients clinical features or outcome.
  
  
  CONCLUSIONS
  We demonstrate that thyroid-stimulating hormone receptor intronic polymorphisms are associated with the susceptibility to Graves' disease and Graves' ophthalmopathy in the Brazilian population, but do not appear to influence the disease course.
authors.affiliation: Laboratory of Cancer Molecular Genetics, School of Medical Sciences (FCM), University of Campinas (UNICAMP), Rua Tessalia Vieira de Camargo, 126, Cidade Universitaria Zeferino Vaz, Campinas, SP, 13083-887, Brazil. bufalo.ne@gmail.com.
authors.forename: N E
authors.initials: NE
authors.lastname: Bufalo
authors.affiliation: Division of Endocrinology, Pontifical Catholic University of Campinas (PUCCAMP), Av. John Boyd Dunlop, s/no Jardim Ipaussurama, Campinas, SP, 13060-904, Brazil.
authors.forename: R B
authors.initials: RB
authors.lastname: Dos Santos
authors.affiliation: Laboratory of Cancer Molecular Genetics, School of Medical Sciences (FCM), University of Campinas (UNICAMP), Rua Tessalia Vieira de Camargo, 126, Cidade Universitaria Zeferino Vaz, Campinas, SP, 13083-887, Brazil.
authors.forename: M A
authors.initials: MA
authors.lastname: Marcello
authors.affiliation: Laboratory of Cancer Molecular Genetics, School of Medical Sciences (FCM), University of Campinas (UNICAMP), Rua Tessalia Vieira de Camargo, 126, Cidade Universitaria Zeferino Vaz, Campinas, SP, 13083-887, Brazil.
authors.forename: R P
authors.initials: RP
authors.lastname: Piai
authors.affiliation: Department of Medical Genetics, University of Campinas (UNICAMP), Rua Tessalia Vieira de Camargo, 126, Cidade Universitaria Zeferino Vaz, Campinas, SP, 13083-887, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: Secolin
authors.affiliation: Division of Endocrinology, Pontifical Catholic University of Campinas (PUCCAMP), Av. John Boyd Dunlop, s/no Jardim Ipaussurama, Campinas, SP, 13060-904, Brazil.|HSPE-IAMSPE, Av. Ibirapuera, 981, Vila Clementino, São Paulo, 04029-000, Brazil.
authors.forename: J H
authors.initials: JH
authors.lastname: Romaldini
authors.affiliation: Laboratory of Cancer Molecular Genetics, School of Medical Sciences (FCM), University of Campinas (UNICAMP), Rua Tessalia Vieira de Camargo, 126, Cidade Universitaria Zeferino Vaz, Campinas, SP, 13083-887, Brazil.
authors.forename: L S
authors.initials: LS
authors.lastname: Ward
mesh_terms: D000328:Adult; D001938:Brazil; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D006111:Graves Disease / Q000235:genetics*; D049970:Graves Ophthalmopathy / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011989:Receptors, Thyrotropin / Q000235:genetics*
chemical_list: D011989:Receptors, Thyrotropin
keywords: Autoimmunity; Graves’ disease; Polymorphisms; Thyroid-stimulating hormone receptor