Ulker M, Yazisiz V, Sallakci N, Avci A B, Sanlioglu S, Yegin O, Terzioglu E
Akdeniz University Teknocity, Kampus Antalya, Turkey.
Int J Immunogenet. 2009 Aug;36(4):245-50. doi: 10.1111/j.1744-313X.2009.00856.x.
Cytotoxic T lymphocyte-associated antigen-4 is a cell-surface molecule providing a negative signal for T cell activation. CTLA-4 gene polymorphisms are known to be related with genetic susceptibility to various autoimmune diseases, including systemic lupus erythematosus (SLE). However, the effects of this polymorphism on clinical features of SLE have not been defined. We analysed the CTLA-4 gene +49 A/G polymorphisms in patients with SLE by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and investigated the effect of polymorphisms on clinical outcomes. Blood was collected from 47 unrelated Turkish SLE patients, all fulfilling the American College of Rheumatology criteria for SLE, and 100 ethnically matched healthy volunteers. The AA genotype was a predominant genotype in the Turkish population and genotype frequencies of CTLA-4 AA were significantly higher in SLE patients (70%) than healthy controls (47%) (P = 0.015). There was a statistically significant difference in the AA genotype [odds ratio (OR): 2.66, confidence interval (CI) 95%: 1.27-5.56, P = 0.014] distribution among patients and controls. There was also an increase in A allele frequency in SLE and controls, but the difference was not statistically significant (81% vs. 70%, P = 0.068, OR = 1.8, CI 95%: 0.99-3.28). Interestingly, mean age and mean age of onset disease was higher in AA homozygote SLE patients compared to non-AA (39.2 +/- 11.5 vs. 31.6 +/- 10.6, P = 0.044; 32.38 vs. 24.31, P = 0.046, respectively). There was no association between genotype and the other clinical features of SLE. Our results suggested that CTLA-4 +49 AA genotype might be a risk factor for the development of SLE in Turkish population and G allele might be involved in early development of SLE. No association with clinical features was found for polymorphism of the promoter region in CTLA-4 +49.
细胞毒性T淋巴细胞相关抗原4是一种细胞表面分子，为T细胞活化提供负信号。已知CTLA-4基因多态性与包括系统性红斑狼疮（SLE）在内的各种自身免疫性疾病的遗传易感性有关。然而，这种多态性对SLE临床特征的影响尚未明确。我们采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析了SLE患者的CTLA-4基因+49 A/G多态性，并研究了多态性对临床结局的影响。收集了47例符合美国风湿病学会SLE标准的无关土耳其SLE患者以及100例种族匹配的健康志愿者的血液。AA基因型是土耳其人群中的主要基因型，SLE患者中CTLA-4 AA的基因型频率（70%）显著高于健康对照（47%）（P = 0.015）。患者和对照之间AA基因型的分布存在统计学显著差异[比值比（OR）：2.66，95%置信区间（CI）：1.27 - 5.56，P = 0.014]。SLE患者和对照中A等位基因频率也有所增加，但差异无统计学意义（81%对70%，P = 0.068，OR = 1.8，95%CI：0.99 - 3.28）。有趣的是，与非AA型SLE患者相比，AA纯合子SLE患者的平均年龄和平均发病年龄更高（分别为39.2±11.5对31.6±10.6，P = 0.044；32.38对24.31，P = 0.046）。基因型与SLE的其他临床特征之间无关联。我们的结果表明，CTLA-4 +49 AA基因型可能是土耳其人群中SLE发病的危险因素，G等位基因可能参与SLE的早期发病。未发现CTLA-4 +49启动子区域多态性与临床特征有关联。
