title: Cytotoxic T-lymphocyte antigen 4 gene polymorphisms in sarcoidosis patients.
abstract: OBJECTIVE
  Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a co-stimulatory molecule that is expressed on activated T-cells, and is an important regulator of T-cell activation in T-cell-dependent immune responses. CTLA-4 signals lead to the downregulation of T-cell proliferation and activation. Sarcoidosis is a systemic granulomatous disorder of unknown etiology, which shows abnormal regulation of T cell activation. Polymorphisms of CTLA-4 have been reported to alter CTLA-4 expression, and are associated with many diseases. In the present study we investigated CTLA-4 polymorphisms of promoter -318(C/T) and exon 1 +49(A/G) in sarcoidosis patients and control subjects to determine whether these genetic variations affect sarcoidosis.
  
  
  METHODS
  One hundred and six sarcoidosis patients and 100 healthy control subjects were studied. The polymerase chain reaction technique and direct genomic sequencing were used to determine the genotypes of promoter -318(C/T) and exon 1 +49(A/G) in the CTLA-4 gene.
  
  
  RESULTS
  We found no difference in the distribution of either genotype between the healthy control subjects and sarcoidosis patients. Among the sarcoidosis patients, the -318(C/T) CC genotype (p = 0.011) and AG or GG genotype at position +49(A/G) (p = 0.004) were increased with ocular involvement compared with those patients without ocular involvement. Furthermore, the +49(A/G) GG genotype was increased in patients with three or more organs affected compared with patients with fewer organs affected (p = 0.019).
  
  
  CONCLUSIONS
  The CTLA-4 polymorphisms are not associated with disease susceptibility of sarcoidosis, but these genetic variations significantly influence phenotypes of sarcoidosis.
authors.affiliation: Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Hattori
authors.forename: Takashi
authors.initials: T
authors.lastname: Niimi
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sato
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Achiwa
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Maeda
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Oguri
authors.forename: Yuji
authors.initials: Y
authors.lastname: Bessho
authors.forename: Hidemi
authors.initials: H
authors.lastname: Ito
authors.forename: Shigeki
authors.initials: S
authors.lastname: Shimizu
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Ueda
mesh_terms: D000069594:Abatacept; D000328:Adult; D000368:Aged; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000235:genetics*; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D049109:Cell Proliferation; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D018796:Immunoconjugates; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012507:Sarcoidosis / Q000235:genetics* / Q000276:immunology*; D017422:Sequence Analysis, DNA; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D000069594:Abatacept