title: Association of CTLA-4 gene polymorphism with Graves' disease and ophthalmopathy in Iranian patients.
abstract: BACKGROUND
  The cytotoxic T lymphocyte associated antigen-4 (CTLA-4) gene, is one of the candidate genes for susceptibility to Graves' disease. This study aimed to investigate the association of Graves' disease and Graves' ophthalmopathy with polymorphisms at position +49 in exon 1 and positions -318 and -1147 in the promoter region of CTLA-4 gene in Iranian patients.
  
  
  METHODS
  A total of 205 unrelated Iranian patients with Graves' disease who were referred to the outpatient endocrine clinic of a large university general hospital and 103 sex-matched healthy controls were included in this study. Venous blood was obtained, genomic DNA was extracted by a salting out method, and the polymorphisms at positions +49, -318 and -1147 of the CTLA-4 gene were determined using the PCR-restriction fragment length polymorphism method (PCR-RFLP). Genotype and allele frequencies were determined.
  
  
  RESULTS
  The frequency of the G allele at position +49 was significantly higher in patients with Graves' disease than in the control group (27.1% vs. 15.1%, OR=2.096, 95%CI=1.350-3.253 and p<0.01). Significant trends were not seen for the other two polymorphisms studied. In patients with ophthalmopathy, the frequency of the G allele at position +49 was higher than in those without ophthalmopathy (33.8% vs. 20.0%, OR=2.043, 95%CI=1.304-3.202 and p<0.01).
  
  
  CONCLUSIONS
  The results of this study suggest that the G allele at position +49 in exon1 of the CTLA-4 gene is associated with Graves' disease and Graves' ophthalmopathy in Iranian patients.
authors.affiliation: Endocrinology and Metabolism Research Center, Vali-Asr hospital, Medical Sciences, University of Tehran, Tehran, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Esteghamati
authors.forename: Omid
authors.initials: O
authors.lastname: Khalilzadeh
authors.forename: Zahra
authors.initials: Z
authors.lastname: Mobarra
authors.forename: Mehdi
authors.initials: M
authors.lastname: Anvari
authors.forename: Maryam
authors.initials: M
authors.lastname: Tahvildari
authors.forename: Hoda Mojazi
authors.initials: HM
authors.lastname: Amiri
authors.forename: Armin
authors.initials: A
authors.lastname: Rashidi
authors.forename: Ghasem
authors.initials: G
authors.lastname: Solgi
authors.forename: Kazem
authors.initials: K
authors.lastname: Parivar
authors.forename: Behrouz
authors.initials: B
authors.lastname: Nikbin
authors.forename: Aliakbar
authors.initials: A
authors.lastname: Amirzargar
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000235:genetics*; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D005091:Exons / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D049970:Graves Ophthalmopathy / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007492:Iran; D008297:Male; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology
chemical_list: D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human