Cytotoxic T-lymphocyte antigen 4 gene polymorphisms in sarcoidosis patients.
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.
Hattori
Noriko
N
Department of Internal Medicine and Molecular Science, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
Niimi
Takashi
T
Sato
Shigeki
S
Achiwa
Hiroyuki
H
Maeda
Hiroyoshi
H
Oguri
Tetsuya
T
Bessho
Yuji
Y
Ito
Hidemi
H
Shimizu
Shigeki
S
Ueda
Ryuzo
R
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*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D018796:Immunoconjugates; D000069594:Abatacept