DU Xiao M, Liu Li W, DU Zhan K, Gu Ruo X, Han Ya L, Wang Xiao Z
Department of Cardiology, Cardiovascular Research Institute, the General Hospital of Shenyang Military, Shenyang, Liaoning, China -
Int Angiol. 2016 Aug;35(4):418-24. Epub 2015 Nov 6.
Chronic inflammation may be involved in pathogenesis of thoracic aortic dissection (TAD). Tumor necrosis factor-alpha (TNF-α) is a proinflammatory cytokine that plays an important role in pathological TAD progression. In this study, we determined wether genetic variants of TNF-α were associated with TAD.
Frequency distributions of TNF-α promoter polymorphisms (-1031C/T,-857C/T,-308G/A, and -238G/A) were determined by direct sequencing. TNF-α plasma levels were measured by enzyme-linked immunosorbent assay. Plasma levels of TNF-α mRNA in peripheral-blood mononuclear cells were analyzed by real-time quantitative polymerase chain reaction amplification.
We found the TNF-α promoter -857C/T polymorphism is associated with disease progression susceptibility in TAD patients. The CC homozygote of TAD patients had a significantly higher risk of TAD than did T allele carriers (P< 0.05). Plasma TNF-α concentrations were also significantly higher in TAD patients than control subjects (P<0.05), and CC genotype carriers showed increased TNF-α levels compared with T allele carriers (P<0.05). Moreover, peripheral-blood mononuclear cells carrying the CC genotype showed increased TNF-α mRNA levels compared with cells carrying the T allele.
The -857C/T polymorphism of TNF-α promoter plays a role in the genetic variation underlying susceptibility of individuals to TAD progression. The CC genotype is associated with increased TNF-α expression in TAD patients, and may be an independent predictive factor for TAD.
慢性炎症可能参与胸主动脉夹层（TAD）的发病机制。肿瘤坏死因子-α（TNF-α）是一种促炎细胞因子，在病理性TAD进展中起重要作用。在本研究中，我们确定TNF-α的基因变异是否与TAD相关。
通过直接测序确定TNF-α启动子多态性（-1031C/T、-857C/T、-308G/A和-238G/A）的频率分布。采用酶联免疫吸附测定法测量TNF-α血浆水平。通过实时定量聚合酶链反应扩增分析外周血单个核细胞中TNF-α mRNA的血浆水平。
我们发现TNF-α启动子-857C/T多态性与TAD患者的疾病进展易感性相关。TAD患者的CC纯合子患TAD的风险显著高于T等位基因携带者（P<0.05）。TAD患者的血浆TNF-α浓度也显著高于对照组（P<0.05），与T等位基因携带者相比，CC基因型携带者的TNF-α水平升高（P<0.05）。此外，与携带T等位基因的细胞相比，携带CC基因型的外周血单个核细胞显示TNF-α mRNA水平升高。
TNF-α启动子的-857C/T多态性在个体对TAD进展易感性的潜在遗传变异中起作用。CC基因型与TAD患者TNF-α表达增加相关，可能是TAD的独立预测因素。
