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International Angiology 2016 August;35(4):418-24


language: English

Association of TNF-α gene variations with thoracic aortic dissection risk in a Chinese Han population

Xiao M. DU 1, 2, Li W. LIU 1, Zhan K. DU 1, Ruo X. GU 1, Ya L. HAN1, Xiao Z. WANG 1

1 Department of Cardiology, Cardiovascular Research Institute, the General Hospital of Shenyang Military, Shenyang, Liaoning, China; 2 Department of Cardiology, 1st People’s Hospital of Shenyang, Liaoning, China

BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.

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