Cytotoxic T lymphocyte associated antigen-4 gene exon 1A49→G polymorphisms confer susceptibility to idiopathic dilated cardiomyopathy  

作　　者：WEI LIU WEI MIN LI CHENG GAO ZHENG WANG RUI HONG ZHANG YI HUI KONG 

机构地区：[1]Department of Cardiology [2]Department of Neurosurgery, First Affiliated Hospital, Harbin Medical University, Harbin, P. R. China

出　　处：《Journal of Microbiology and Immunology》2005年第2期131-135,共5页中华微生物学和免疫学（英文版）

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 CTIA-4 gene exon 1 A49→G polymorphism with susceptibility to IDC in Han Chinese and its influences on serum soluble CTIA-4 （sCrLA-4） and Th1/Th2 cytokine bias. Polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） techniques were used to analyze the dimorphism of CTL4-4 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 sCTIA-4 was found in the 1DC group compared with the controls [ （ 1.87 ± 1.06） μg/L vs. （0.54 ± 0.19） 〉g/L, P 〈 0.05 ~. 1FN-7 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 I （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 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 s

关 键 词：Idiopathic dilated cardiomyopathy CTLA-4 Polymorphism Restriction fraonent lengthAutoimmune Th 

分 类 号：R542.2[医药卫生—心血管疾病]