title: Herpesvirus type 7 infection may play an important role in individuals with a genetic profile of susceptibility to Graves' disease.
abstract: OBJECTIVE
  An inherited profile of genes related to the response to aggressive environmental factors such as viruses and chemicals may be related to an increased susceptibility to Graves' disease (GD).
  
  
  METHODS
  This prospective case-control study was designed to examine the relationship between human herpesviruses (HHV) infection, determined by circulating DNA; tumour protein p53 (TP53) apoptotic ability; and detoxification system genes, and GD. We studied 280 confirmed GD patients paired to 284 controls with respect to environmental exposure. Exclusion criteria included medications that could interfere with thyroid function evaluation and a recent history of viral and bacterial infections.
  
  
  RESULTS
  A stepwise regression analysis adjusted for age, gender, and ethnicity established the inheritance of glutathione S-transferase pi 1 (GSTP1) (odds ratio (OR)=3.423; 95% confidence interval (CI)=2.120-5.527; P<0.001) and cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) variants (OR=1.649; 95% CI=1.012-2.686; P=0.0445) as significant risk factors for the disease. HHV-7 infection was much more common in GD patients (64.64%) than in controls (38.73%; chi(2), P<0.0001), and it increased the risk for GD more than three times (OR=3.133; 95% CI=1.959-5.011; P<0.0001). The inheritance of less efficient Pro/Pro TP53 gene variants significantly increased the risk of GD development (OR=5.196; 95% CI=2.112-12.783; P<0.0001) and also favored HHV-7 infection (OR=2.835; 95% CI=1.100-7.310; P=0.0275). In addition, 72TP53 variants augmented the risk of GD relapse (OR=1.860; 95% CI=1.015-3.410; P=0.0446).
  
  
  CONCLUSIONS
  We suggest that an inherited genetic profile involving TP53 may favor HHV-7 infection and maintenance, which, in turn, may initiate and perpetuate GD autoimmune process.
authors.affiliation: Laboratory of Cancer Molecular Genetics, Faculty of Medical Sciences School, State University of Campinas (Unicamp), PO Box 6111, Campinas, São Paulo, Brazil.
authors.forename: Janaina Luisa
authors.initials: JL
authors.lastname: Leite
authors.forename: Natassia Elena
authors.initials: NE
authors.lastname: Bufalo
authors.forename: Roberto Bernardo
authors.initials: RB
authors.lastname: Santos
authors.forename: João Hamilton
authors.initials: JH
authors.lastname: Romaldini
authors.forename: Laura Sterian
authors.initials: LS
authors.lastname: Ward
mesh_terms: D000328:Adult; D015551:Autoimmunity; D016022:Case-Control Studies; D003520:Cyclophosphamide / Q000031:analogs & derivatives; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006111:Graves Disease / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D016199:Herpesvirus 7, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012008:Recurrence; D012043:Regression, Psychology; D012307:Risk Factors; D019349:Roseolovirus Infections / Q000453:epidemiology* / Q000276:immunology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D055815:Young Adult
chemical_list: D003520:Cyclophosphamide; D019363:Cytochrome P-450 CYP1A1; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D016159:Tumor Suppressor Protein p53; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human; C003726:trofosfamide