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  • Title: Effects of tumor necrosis factor gene polymorphisms on patients with congestive heart failure. VEST Investigators for TNF Genotype Analysis. Vesnarinone Survival Trial.
    Author: Kubota T, McNamara DM, Wang JJ, Trost M, McTiernan CF, Mann DL, Feldman AM.
    Journal: Circulation; 1998 Jun 30; 97(25):2499-501. PubMed ID: 9657468.
    Abstract:
    BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is known to be elevated in patients with congestive heart failure (CHF). Two biallelic polymorphisms have been identified in the TNF gene locus: one in the promoter region of TNF-alpha (TNFA1/2), and the other in the first intron of TNF-beta (TNFB1/2). Both TNFA2 and TNFB2 alleles are associated with high TNF-alpha production in vitro and susceptibility to inflammatory diseases. Given the importance of TNF-alpha in the pathogenesis of CHF, we studied the prevalence of TNF gene polymorphisms in CHF patients and the correlation of genotypes to in vivo TNF-alpha levels. METHODS AND RESULTS: TNFA and TNFB genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism technique. There were no differences in the TNF allele frequencies between CHF (n=229; TNFA1/2=0.84/0.16, TNFB1/2=0.33/0.67) and control subjects (n=139; TNFA1/2=0.84/0.16, TNFB1/2=0.32/0.68). In 211 patients with CHF, circulating levels of TNF-alpha and the soluble receptors type I and type II were measured by ELISA: 6.18+/-3.59 pg/mL, 1768+/-761 pg/mL, and 4484+/-1750 pg/mL, respectively. There were no correlations between TNFA or TNFB genotypes and circulating levels of TNF-alpha or its soluble receptors in the CHF patients. CONCLUSIONS: Despite their association with other inflammatory diseases, neither TNFA nor TNFB polymorphisms are related to the presence of CHF or the elevation of circulating TNF-alpha. Thus, other factors may be more important in determining the circulating levels of TNF-alpha in CHF.
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