摘要
目的探讨细胞毒性T淋巴细胞相关抗原4(CTLA4)基因外显子1A49→G多态性与特发性扩张型心肌病(IDC)遗传易感性的关系。方法采用聚合酶链反应限制性片段长度多态性(PCRRFLP)分析IDC(48例)及正常对照(50名)CTLA4基因外显子49位点A→G多态性;ELISA检测血清sCTLA4,IFNγ及IL4水平,以IFNγ/IL4比值作为Th1/Th2偏离指标。结果IDC组GG基因型和G等位基因频率显著高于对照组(P=0.012,P=0.008);IDC组与对照组相比sCTLA4水平较高(1.87μg/L±1.06μg/L,0.54μg/L±0.19μg/L,P<0.05);IFNγ水平较低(16ng/L±6ng/L,30ng/L±10ng/L,P<0.05);IFNγ/IL4比值较低(1.63±0.50,3.01±0.89,P<0.05);两组间IL4差异无统计学意义。IDC组GG基因型及G等位基因频率与sCTLA4水平(r=0.57,P=0.021)及IFNγ/IL4比值(r=0.42,P=0.028)相关。结论CTLA4基因外显子A49→G多态性与IDC易感性相关。
Objective To investigate the association of cytotoxic T lymphocyte associated antigen-4 （CTLA-4） gene exon 1 A49→G pol.ymorphism with the genetic susceptibility to idiopathic dilated cardiomyopathy （IDC） in Chinese Han nationality. Methods Peripheral blood samples were collected from 48 patients with IDC, 31 fames and 17 females, and 50 sex- and age-matched normal controls. ELISA was used to examine the cytokines： sCTLA-4, γ-interferon （IFN-γ）, and interleukin-4 （IL-4）with the ratio of IFN-γ/IL--4 as an indicator for Th1/Th2 bias. PCR-RFLP was used to analyze the A/G polymorphism of CTLA-4 exon 1 A49→G. The relationship of CTLA-4 genotype and alleles frequencies with sCTLA-4, IFN-γ and IFN-γ/IL-4 was evaluated by linear regression analysis. Results Compared with the normal controls, the frequencies of GG genotype （0. 6042 and 0. 7396, P =0.012） and the G allele （0.36 and 0.56, P = 0. 008） were significantly increased in the patients with IDC. Increased serum sCTLA-4 was found in the IDC group compared with the controls （ 1.87 μg/L ± 1.06 μg/L vs. 0.54 μg/L ± 0.19 μg,/L, P 〈 0.05 ）. IFN-γ/ was significantly lower in the IDC group than in the control group （ 16 ng/L ±6 ng/L vs. 30 ng/L ± 10 ng/L,P 〈0.05）. The ratio of IFN-γ/IL-4 was significantly in the IDC group than in the control group （ 1.63 ± 0.50 vs. 3.01 ± 0.89, P 〈 0.05）. No statistically difference was found in the IL-4 level between the two groups. Linear regression analysis manifested significant interrel.ationship between the GG genotype, G allele frequencies and serum sCTLA-4 （ r = 0.57, P = 0. 021 ）, IFN-γ/IL-4 ratio （ r = 0.42, P = 0.028 ） in the IDC group. While no correlation was found for AA, AG genotype and the A allele frequency. Conclusion CTLA-4 gene exon 1 A49 → G substitution is associated with an increased IDC genetic susceptibility, which implicates that the CTLA-4 gene may have a significant role in IDC, possibly via a Thr→Ala change in CTLA-d signal peptide, wi
出处
《中华医学杂志》
CAS
CSCD
北大核心
2005年第45期3221-3224,共4页
National Medical Journal of China
关键词
心肌病
充血性
T淋巴细胞
细胞毒性
多态性
限制性片段长度
Cardiomyopathy, congestive
T-lymphocytes, cytotoxic
Polymorphism, restriction fragment length
