title: Cytotoxic T lymphocyte antigen 4 (CTLA-4) dimorphism in patients with systemic lupus erythematosus.
abstract: OBJECTIVE
  Genetic susceptibility to systemic lupus erythematosus (SLE) is conferred not only by various genes within the major histocompatibility complex (MHC) region, but also by several other non-MHC linked genes. The negatively signalling molecule CTLA-4 is involved in establishing and maintaining of peripheral T cell tolerance, which controls T cell activation and reactivity. Its attenuating action helps to prevent an inappropriate initiation of T cell responses to self antigens and to terminate ongoing T cell responses. We tested if there was an association between CTLA-4 and SLE, a disease with B and T cell hyperreactivity and impaired peripheral T cell tolerance.
  
  
  METHODS
  Using the polymerase chain reaction--restriction fragment length polymorphism method with Bbv I digestion, we assessed an exon 1 transition dimorphism (49 A/G) of the CTLA-4 gene in 102 SLE patients and in 76 healthy controls.
  
  
  RESULTS
  The distribution of CTLA-4 exon 1 genotypes in the SLE group was significantly different from that in the controls (chi 2 = 6.178, p < 0.05). 17.6% of the SLE patients were G/G homozygotes compared to 5.3% of the controls; 36.3% were A/G heterozygotes vs 40.8% of controls; and 46.1% were A/A homozygotes vs 53.9% of the controls. The frequency of the G allele was significantly higher in SLE patients (35.8%) than in controls (25.7%; chi 2 = 4.142, p = 0.042).
  
  
  CONCLUSIONS
  Our results indicate that the non-MHC linked CTLA-4 gene could confer susceptibility in SLE, as it does in various other autoimmune diseases (Hashimoto thyroiditis, Graves' disease, IDDM).
authors.affiliation: Medical Clinic II, Martin Faculty Hospital, Jessenius Medical Faculty, Martin, Slovak Republic. pullmann@sco.medicalh.sk
authors.forename: R
authors.initials: R
authors.lastname: Pullmann
authors.forename: J
authors.initials: J
authors.lastname: Lukác
authors.forename: M
authors.initials: M
authors.lastname: Skerenová
authors.forename: J
authors.initials: J
authors.lastname: Rovensky
authors.forename: J
authors.initials: J
authors.lastname: Hybenová
authors.forename: V
authors.initials: V
authors.lastname: Melus
authors.forename: S
authors.initials: S
authors.lastname: Celec
authors.forename: R
authors.initials: R
authors.lastname: Pullmann
authors.forename: R
authors.initials: R
authors.lastname: Hyrdel
mesh_terms: D000069594:Abatacept; D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D060908:CTLA-4 Antigen; D004247:DNA / Q000032:analysis; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D018796:Immunoconjugates; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D017931:DNA Primers; D018796:Immunoconjugates; D000069594:Abatacept; D004247:DNA