title: HLA-G 3' untranslated region polymorphic sites associated with increased HLA-G production are more frequent in patients exhibiting differentiated thyroid tumours.
abstract: BACKGROUND
  HLA-G is a nonclassical class I histocompatibility molecule implicated on the immune escape mechanism of tumour cells. We evaluated the genetic diversity of HLA-G 3' untranslated region (3'UTR) and associated polymorphic sites with clinical presentation and with the magnitude of HLA-G thyroid expression.
  
  
  METHODS
  Polymorphic sites at 3'UTR (14bpINS/DEL, +3003C/T, +3010C/G, +3027A/C, +3035C/T, +3142C/G, +3187A/G, +3196C/G) were characterized by sequencing analyses in blood samples of 72 patients exhibiting papillary thyroid carcinoma (PTC), 22 follicular thyroid carcinomas (FTC), 19 follicular adenomas (FA), 21 colloid goitres and 156 healthy controls.
  
  
  RESULTS
  Compared to goitre and/or controls, patients with PTC exhibited higher frequency of 14bpDEL (P = 0·030), +3010G (P = 0·034), +3010CG (P = 0·044), +3142CG (P = 0·040), +3035C (P = 0·050) and +3187GG (P = 0·032). Patients with FTC presented higher frequency of 14bpINS/DEL (P = 0·020). The UTR-5 haplotype was underrepresented in PTC (P = 0·050). The +3003TT was more frequent in patients with PTC older than 45 years (P = 0·030). Male patients had a higher frequency of +3196GG (P = 0·040). Tumour multicentricity was associated with UTR-2 (P = 0·030). The following associations were observed in PTC and FTC combined: i) tumour size <2 cm with 14bpINS/INS (P = 0·030); ii) multicentricity with +3035CC (P = 0·030) and +3196GG (P = 0·030); iii) decreased thyroid HLA-G expression with +3196C and +3196CC; and iv) moderate HLA-G thyroid staining with UTR-2.
  
  
  CONCLUSIONS
  HLA-G 3'UTR polymorphisms associated with a greater magnitude of HLA-G production were associated with differentiated thyroid tumours and with variables implicated in poor prognosis. These findings corroborate the unfavourable role of HLA-G in thyroid cancer.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Nathalie Lobo
authors.initials: NL
authors.lastname: de Figueiredo-Feitosa
authors.affiliation: Program of Basic and Applied Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.|Division of Clinical Immunology, Department of Internal Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Martelli Palomino
authors.affiliation: Program of Basic and Applied Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil.|Division of Clinical Immunology, Department of Internal Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Daiani Cristina
authors.initials: DC
authors.lastname: Cilião Alves
authors.affiliation: Department of Chemistry, School of Philosophy, Sciences and Letters of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Celso Teixeira
authors.identifier: http://orcid.org/0000-0002-7337-1203
authors.initials: CT
authors.lastname: Mendes Junior
authors.affiliation: Division of Clinical Immunology, Department of Internal Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Eduardo Antonio
authors.initials: EA
authors.lastname: Donadi
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Léa Maria Zanini
authors.initials: LM
authors.lastname: Maciel
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000328:Adult; D000368:Aged; D002277:Carcinoma / Q000235:genetics; D002291:Carcinoma, Papillary; D016022:Case-Control Studies; D005260:Female; D059951:HLA-G Antigens / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D017422:Sequence Analysis, DNA; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000276:immunology / Q000473:pathology
chemical_list: D020413:3' Untranslated Regions; D059951:HLA-G Antigens