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

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.