摘要:Autoimmune mechanisms, including cellular and humoral immune, are likely to participate in the pathogenesis of at least a subgroup of idiopathic dilated cardiomyopathy (IDC), in which cellular immune-mediation plays a more important role. Cytotoxic T lymphocyte associated antigen-4 (CTLA-4) is the major negative regulatory factor of cellular immunity. This study was conducted to investigate the association of CTLA-4 gene exon 1 A49→G polymorphism with susceptibility to IDC in Han Chinese and its influences on serum soluble CTLA-4 (sCTLA-4) and Th1/Th2 cytokine bias. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques were used to analyze the dimorphism of CTLA-4 exon 1 in the unrelated Han ethnic population in Heilongjiang Province (including 48 IDC patients and 50 normal controls). Serum sCTLA-4, IFN-γ and IL-4 were evaluated by ELISA, with the ratio of IFN-γ/IL-4 as indicator for Th1/Th2 bias. Compared with controls, the frequencies of GG genotype (0.6042 and 0.3600, P=0.012) and the G allele (0.7396 and 0.5600, P=0.008) were significantly increased in IDC patients. Increased serum sCTLA-4 was found in the IDC group compared with the controls [(1.87±1.06) μg/L vs. (0.54±0.19) μg/L, P<0.05]. IFN-γ was much lower in IDC patients than that of the controls [(16.38±6.25) ng/L vs. (29.81±10.66) ng/L (P<0.05)], whereas no statistical difference of IL-4 was found between the two groups [(12.85±1.86) ng/L vs. (12.11±2.76) ng/L], so the ratio of IFN-γ/IL-4 declined significantly (1.63±0.50 vs. 3.01±0.89, P<0.05). Linear regression analysis manifested a significant interrelationship between the GG genotype, G allele frequencies and serum sCTLA-4, IFN-γ/IL-4 in the IDC group (r=0.57, P=0.021 and r=0.32, P=0.036). CTLA-4 gene A49→G substitution was associated with an increased IDC risk, which implicated that the CTLA-4 gene exon 1 may have a considerable role in autoimmune cardiac damage, possibly via a Thr→Ala change in signal peptide, which influences the protein synthesis and modification processes, with a result of functional alteration of sCTLA-4. The bias of Th1/Th2 paradigm was associated with the increased sCTLA-4 under certain background of immunogenetics.