CTLA4 gene polymorphisms and soluble CTLA4 protein in Behcet's disease.
Park, KS; Baek, JA; Do, JE; Bang, D; Lee, ES
Tissue antigens, 74(3):222-227, 2009
Cytotoxic T lymphocyte antigen 4 (CTLA4; CD152) is a costimulatory molecule expressed on activated T cells that plays a key inhibitory role during T lymphocyte activation. The gene encoding for CTLA4 has been suggested as a candidate for conferring susceptibility to autoinflammatory diseases. We investigated the polymorphisms of the CTLA4 gene [promoter region (-1722 T/C, -1661 A/G and -318 C/T) and exon 1 (+49 G/A)] and the differences of serum soluble sCTLA4 levels in 285 patients with Behcet's disease (BD) and 287 controls. The frequency of the CTLA4 -1661 GG genotype was significantly higher in BD patients than in controls [P = 0.019, odds ratio (OR) = 5.2, 95% confidence interval (CI) = 1.13-23.86]. Also, the genotype frequency for CTLA4 -1722 TC was significantly higher (P = 0.014, OR = 1.8, 95% CI = 1.13-2.99), while CTLA4 -1722 CC was significantly lower (P = 0.018, OR = 0.4, 95% CI = 0.20-0.87) in BD patients with ocular lesions compared with patients without this symptom. Serum sCTLA4 levels in BD patients were significantly lower, especially in BD patients with the CTLA4 +49 G allele, than those in healthy controls (P < 0.05). Although our understanding of the role of the CTLA4 gene and its protein product in BD is incomplete, these results suggest that single nucleotide polymorphisms of the promoter and exon regions in the CTLA4 gene are candidates that predispose to BD and that sCTLA4 may be related to the immunological abnormalities and disease expressions associated with BD.
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