中国人CTLA-4基因-1722位点多态性与系统性红斑狼疮的相关性

Association of CTLA-4 promoter -1722 polymorphism with systemic lupus erythematosus in Chinese

目的研究细胞毒性T淋巴细胞相关抗原4 (cytotoxic T lymphocyte-associated antigen 4, CTLA-4)基因启动子区-1722位点(T/C)多态性在中国南方地区汉族人群中的分布及其与系统性红斑狼疮(SLE)的相关性。方法103例患者诊断均符合1982年美国风湿病学会修订的SLE分类标准,其中男13例,女90例。正常对照组110例,其中男21例,女89例。全部研究对象均为无血缘关系的中国南方汉族人群。采用微量全血提取法,从EDTA抗凝血中提取DNA。应用聚合酶链反应(PCR)-限制性片段长度多态性(RFLP)方法,对所有SLE患者和正常对照者进行CTLA-4基因-1722位点多态性检测。结果CTLA-4基因-1722位点多态性在中国南方地区人群中普遍存在,与正常对照组比较,SLE患者CTLA-4基因-1722位点TC基因型频率明显升高(42% vs58%,P<0.05), CC基因型频率明显降低(25% vs15%,P<0.05),TT基因型频率虽有降低趋势,但差异无显著性(33% vs27%,P>0.05);而SLE患者等位基因频率和携带者频率分布均无显著性差异(P>0.05)。在不同人种CTLA-4基因-1722位点基因型频率和等位基因频率分布存在差异。结论CTLA-4基因-1722位点多态性与SLE明显相关,CTLA-4基因可能是SLE的易感基因。

Objective To investigate the possible association of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) promoter -1722 polymorphism with systemic lupus erythematosus (SLE) in the population in southern China. Methods A total of 103 SLE patients (13 males and 90 females with an average age of 33.63±12.58 years) diagnosed according to the SLE diagnostic criteria of the American College of Rheumatology revised in 1982 and 110 healthy ethnically matched controls (21 males and 89 females with an average age of 27.49±8.60 years), all from southern China, were enrolled in the study. DNA was extracted from EDTA-treated blood samples according to the standard isolation procedure. The restriction fragment length polymorphism-polymerase chain reaction was used to analyze CTLA-4 promoter-1722 polymorphism in SLE patients and healthy controls. Results Compared with the controls, the SLE patients had higher frequencies of TC genotype (42% vs 58%, P<0.05) and lower frequency of CC genotype (25% vs 15%, P<0.05). There were no significant differences in the frequencies of TT genotype, alleles and phenotypes between SLE patients and controls; however, significant differences in the frequencies of TT genotype and alleles of CTLA-4 promoter -1722 were found among different races (P<0.05). Conclusion CTLA-4 promoter -1722 polymorphism appears to be associated with SLE susceptibility in southern Chinese population.