摘要
目的探讨特发性扩张型心肌病(idiopathicdilatedcardiomyopathy,IDC)患者细胞毒性T淋巴细胞相关抗原-4(cytotoxicTlymphocyteassoccatedantigen4,CTLA-4)表达状况及由CTLA-4基因启动子区单核苷酸多态性(singlenucleotidepolymorphism,SNP)导致的不同遗传易感性机制。方法采用限制性片段长度多态性分析151例IDC患者,120名正常健康人CTLA-4基因启动区-1772、-1661及-318位点SNP;免疫酶联吸附测定法检测血清sCTLA-4、干扰素-γ及白介素-4水平;综合分析CTLA-4启动区基因型、等位基因频率及与sCTLA-4、干扰素-γ/白介素-4的相关性。结果IDC患者sCTLA-4水平与CTLA-4基因启动区SNP相关,携带-1772T/C变异者sCTLA-4表达增高。-1772TC基因型频率在IDC组尤其低射血分数亚组显著高于对照组,IDC组-1661G和-1661GG频率显著降低,具有-1772TC-1661AA及-1772TC-1661AG单倍型IDC患者sCTLA-4显著升高。结论IDC患者CTLA-4表达异常,CTLA-4基因启动区-1772C/T和-1661A/GSNP与IDC遗传易感性相关。-1772T/C变异可能影响CTLA-4基因剪接,干扰蛋白表达和功能,阻止负性调节信号传递而导致对IDC的易感。
Objective To investigate the expression of cytotoxic T lymphocyte associated antigen-4 （CTLA-4） in patients with idiopathic dilated cardiomyopathy （IDC） and to explore genetic susceptibility to IDC caused possibly by single nucleotide polymorphism （SNP） of CTLA-4 gene promoter. Methods PCR-restriction fragment length polymorphism techniques were used to analyze the SNPs of CTLA-4 gene at position - 1772, - 1661 and -318 in the promoter region. Serum sCTLA-4, IFN-γ/and IL-4 were tested by ELISA. Results sCTLA-4 levels of IDC patients were associated with the haplotype and genotype. Patients with - 1772 TC genotype or - 1772 TC - 1661 AA, - 1772 TC - 1661 AG haplotypes had higher sCTLA-4 levels than patients with other haplotypes did. The frequency of - 1772 TC genotype was significantly high in patients with low ejection factor（EF） values. Whereas the frequencies of - 1661 G allele and - 1661 GG genotype were lower in IDC patients. Levels of IL-4 were increased in IDC group. Condusion Patients with IDC have an aberrant expression of the CTLA-4 products, and the - 1772 C/T and - 1661 A/G polymorphisms. The two SNPs may function as genetic markers for disease susceptibility.
出处
《中华医学遗传学杂志》
CAS
CSCD
北大核心
2006年第2期198-201,共4页
Chinese Journal of Medical Genetics
基金
哈尔滨医科大学研究生创新基金(2005)~~
