Department of Cardiology, Fuwai Hospital and Cardiovascular Institute, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
J Rheumatol. 2011 Dec;38(12):2602-7. doi: 10.3899/jrheum.110231. Epub 2011 Oct 1.
Tumor necrosis factor-α (TNF-α) is a multifunctional proinflammatory cytokine that influences the pathogenesis of Takayasu arteritis (TA). There is still no evidence of the relationship between TNF-α gene promoter polymorphisms and TA. We examined whether variations in the TNF-α promoter region may lead to TA susceptibility and disease progression.
Five TNF-α gene promoter polymorphisms (-238G/A, -308G/A, -857C/T, -863C/A, and -1031C/T) were analyzed in 110 Chinese Han patients with TA, with a control group of 362 unrelated healthy individuals. Genotypes of TNF-α gene promoter polymorphisms were identified by direct sequencing. TNF-α plasma concentrations were determined by ELISA.
Our results indicated that the frequency of the -863A allele was significantly lower in the patients with TA than in the controls (18.2% vs 25.7%; p = 0.011), but the significance was lost after Bonferroni correction (p(c) = 0.055). The frequency of -863CA/AA genotypes was significantly lower in the patients with refractory TA than in those with the 863CC genotype (22.4% vs 44.2%; p(c) < 0.01). The frequency of the GGCCT haplotype was significantly higher in patients than in the controls, while the frequencies of GGCAT and GGCCC haplotypes were significantly lower in patients than in controls. The plasma TNF-α concentrations were significantly lower in the subjects carrying the -863A allele than in those without. Patients with active TA had a significant increase in plasma levels of TNF-α compared with remission patients and the control group.
Polymorphisms of the TNF-α promoter are not associated with TA in the Chinese Han population. The A allele of the -863C/A polymorphism is associated with decreased TNF-α expression, which might affect medical treatment.
肿瘤坏死因子-α（TNF-α）是一种多功能的促炎细胞因子，影响 Takayasu 动脉炎（TA）的发病机制。目前尚无 TNF-α 基因启动子多态性与 TA 之间关系的证据。我们研究了 TNF-α 启动子区域的变异是否可能导致 TA 的易感性和疾病进展。
我们分析了 110 例汉族 TA 患者和 362 名无关健康个体的 TNF-α 基因启动子 5 个多态性（-238G/A、-308G/A、-857C/T、-863C/A 和 -1031C/T）。通过直接测序确定 TNF-α 基因启动子多态性的基因型。通过 ELISA 测定 TNF-α 血浆浓度。
我们的结果表明，与对照组相比，TA 患者中 -863A 等位基因的频率明显较低（18.2%比 25.7%；p=0.011），但经 Bonferroni 校正后失去了显著性（p(c)=0.055）。难治性 TA 患者中 -863CA/AA 基因型的频率明显低于 863CC 基因型（22.4%比 44.2%；p(c)<0.01）。与对照组相比，患者中 GGCCT 单倍型的频率明显较高，而 GGCAT 和 GGCCC 单倍型的频率明显较低。携带 -863A 等位基因的个体血浆 TNF-α 浓度明显低于不携带该等位基因的个体。与缓解期患者和对照组相比，活动期 TA 患者的血浆 TNF-α 水平显著升高。
TNF-α 启动子多态性与中国汉族人群的 TA 无关。-863C/A 多态性的 A 等位基因与 TNF-α 表达减少有关，这可能影响治疗。
