PMID- 9657468 OWN - NLM STAT- MEDLINE DCOM- 19980715 LR - 20220317 IS - 0009-7322 (Print) IS - 0009-7322 (Linking) VI - 97 IP - 25 DP - 1998 Jun 30 TI - Effects of tumor necrosis factor gene polymorphisms on patients with congestive heart failure. VEST Investigators for TNF Genotype Analysis. Vesnarinone Survival Trial. PG - 2499-501 AB - 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. FAU - Kubota, T AU - Kubota T AD - Division of Cardiology, University of Pittsburgh Medical Center, PA 15213, USA. FAU - McNamara, D M AU - McNamara DM FAU - Wang, J J AU - Wang JJ FAU - Trost, M AU - Trost M FAU - McTiernan, C F AU - McTiernan CF FAU - Mann, D L AU - Mann DL FAU - Feldman, A M AU - Feldman AM LA - eng PT - Journal Article PT - Multicenter Study PT - Research Support, Non-U.S. Gov't PL - United States TA - Circulation JT - Circulation JID - 0147763 RN - 0 (DNA Primers) RN - 0 (Lymphotoxin-alpha) RN - 0 (Tumor Necrosis Factor-alpha) SB - IM MH - Adult MH - Case-Control Studies MH - DNA Primers MH - Disease Susceptibility MH - Female MH - Genotype MH - Heart Failure/*blood/*genetics MH - Humans MH - Lymphotoxin-alpha/blood/genetics MH - Male MH - Middle Aged MH - *Polymorphism, Genetic MH - Severity of Illness Index MH - Tumor Necrosis Factor-alpha/*genetics/*metabolism EDAT- 1998/07/10 00:00 MHDA- 1998/07/10 00:01 CRDT- 1998/07/10 00:00 PHST- 1998/07/10 00:00 [pubmed] PHST- 1998/07/10 00:01 [medline] PHST- 1998/07/10 00:00 [entrez] AID - 10.1161/01.cir.97.25.2499 [doi] PST - ppublish SO - Circulation. 1998 Jun 30;97(25):2499-501. doi: 10.1161/01.cir.97.25.2499.