科研之友
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摘要
BACKGROUND: Chronic inflammation may be involved in pathogenesis of thoracic aortic dissection (TAD). Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine that plays an important role in pathological TAD progression. In this study, we determined wether genetic variants of TNF-alpha were associated with TAD. METHODS: Frequency distributions of TNF-alpha promoter polymorphisms (-1031C/T,-857C/T,-308G/A, and-238G/A) were determined by direct sequencing. TNF-alpha plasma levels were measured by enzyme-linked immunosorbent assay. Plasma levels of TNF-alpha mRNA in peripheral-blood mononuclear cells were analyzed by real-time quantitative polymerase chain reaction amplification. RESULTS: We found the TNF-alpha 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-alpha concentrations were also significantly higher in TAD patients than control subjects (P<0.05), and CC genotype carriers showed increased TNF-alpha levels compared with T allele carriers (P<0.05). Moreover, peripheral-blood mononuclear cells carrying the CC genotype showed increased TNF-alpha mRNA levels compared with cells carrying the T allele. CONCLUSIONS: The-857C/T polymorphism of TNF-alpha promoter plays a role in the genetic variation underlying susceptibility of individuals to TAD progression. The CC genotype is associated with increased TNF-alpha expression in TAD patients, and may be an independent predictive factor for TAD.
- 出版日期2016-8
- 单位中国人民解放军沈阳军区总医院
