CTLA-4基因多态性与特发性扩张型心肌病的相关性  

Relationship of CTLA-4 polymorphisms with susceptibility for idiopathic dilated cardiomyopathy

作　　者：刘英[1] 刘巍[2] 李为民[2] 李悦[2] 孔一慧[2] 甘润韬[2] 王政[2] 樊瑛[2] 耿建强[2] 邵群[2] 张美[2] 高成[3] 王秀荣 

机构地区：[1]哈尔滨医科大学第四临床医学院检验科,黑龙江150001 [2]哈尔滨医科大学第一临床医学院心内科,黑龙江150001 [3]哈尔滨医科大学第四临床医学院神经外科,黑龙江150001 [4]哈尔滨兽医研究所生物技术国家重点实验室,黑龙江150001

出　　处：《中国免疫学杂志》2007年第1期66-69,共4页Chinese Journal of Immunology

摘　　要：目的：包括细胞和体液免疫在内的自身免疫机制至少参与了部分特发性扩张型心肌病（Idiopathic dilated cardiomyopathy，IDC）患者的发病，且前者介导的心肌损害在IDC中更重要。CTLA-4是特异性细胞免疫的负性调节因子。本研究旨在探讨CTLA-4基因启动子-318C／T、外显子A／G多态性及3＇非翻译区（AT）n微卫星多态性与IDC及血清可溶性CTLA-4（sCTLA-4）水平的相关性。方法：采用聚合酶链反应-限制性片段长度多态性（Polymerase chain reaction—restriction fragment length polymorphisms，PCR-RFLP）方法分析黑龙江省无血缘关系汉族人群（包括72例IDC患者，100例正常健康人）CTLA-4基因-318C／T、49位点A／G多态性及3’微卫星多态性；ELISA法检测血清sCTLA-4水平。综合分析CTLA-4基因型频率、等位基因频率与IDC及sCTLA-4水平的相关性。结果：IDC组外显子1GG基因型和G等位基因频率显著高于正常对照组（P=0．012，P：0．008）；3’非翻译区共发现18种等位基因，106bp等位基因频率在IDC患者中显著增高（22.22％vs1％，P=0.0002，OR=23．56，95％CI：9．65—83．74）；两组间-318C／T多态性分布无统计学差异。与对照组相比，IDC组sCTLA-4水平显著升高[（1．87±1．06）μg/L比（O．54±0．19）μg/L，P〈0．05]；直线回归分析显示，IDC组GG基因型及G等位基因频率与血清sCTLA-4水平（r=0．57，P=0．021）显著相关，而AA、A／G基因型及A等位基因频率与sCTLA-4水平无相关性。启动子-318C／T多态性及3’非翻译区（AT）n微卫星多态性与sCTLA-4水平的亦无相关性。结论：CTLA-4基因外显子1A49-G变异与IDC相关，携带G等位基因者易患IDC，其机制可能为该多态性造成CTLA-4信号肽中编码苏氨酸和甘氨酸的替换，从而影响蛋白翻译后加工、修饰，使sCTLA-4功能发生变化。提示3’末端非翻译区（AT）n重复序列中106bp等位基因可能是IDC的易感�Objective：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-mediated one 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 promoter -318C/T polymorphism, exon 1 A/G polymorphism and 3＇ untranslated region micresatellite polymorphism with susceptibility to IDC in Han Chinese. Methods：Polymerase chain reaction-restriction fragment length polymorphisms（PCR-RFLP） techniques were used to analyze the polymorphisms of CTLA-4 promoter -318, exon 1 A/G and 3＇ untranslated region in the unrelated Han ethnic population in Heilongjiang Province（ including 72 IDC patients and 100 normal controls）. Serum sCTLA-4 was tested by ELISA. The relationship of CTLA-4 genotypo and alleles frequencies with sCTLA-4 was evaluated by linear regression analysis. Results：Compared with controls, the frequencies of GG genotype（0. 604 2 and 0. 739 6, P = 0. 012） and the G allele（0. 360 0 and 0. 560 0, P =0. 008） were significantly increased in patients with IDC. 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]. Eighteen alleles of CTLA-4 micresatellite were found in IDC patients and healthy individuals. Long allele, 106 bp was apparently increased in patients with IDC compared with healthy controls（22. 22% vs 1%, P =0. 000 2, OR =23. 56, 95% CI： 9. 65-83. 74）. Linear regression analysis manifested a significant interrelationship between the GG genotypo, G allele frequencies and serum sCTLA-4 （r = 0. 57, P = 0. 021 ）. Conclusion：CTLA-4 gene exon 1 A49→G substitution is associated with an increased IDC risk, and ＂G＂ allele carriers had significantly increased IDC risk, which implicated that

关 键 词：特发性扩张型心肌病 CTLA-4 限制性片段长度多态性 自身免疫 

分 类 号：R392.13[医药卫生—免疫学] R542.2[医药卫生—基础医学]