EFFECTS OF TUMOR-NECROSIS-FACTOR GENE POLYMORPHISMS ON PATIENTS WITH CONGESTIVE-HEART-FAILURE

Background-Tumor necrosis factor-alpha (TNF-alpha) is known to be elev ated in patients with congestive heart failure (CHF). Two biallelic po lymorphisms have been identified in the TNF gene locus: one in the pro moter region of TNF-alpha (TNFA1/2), and the other in the first intron of TNF-beta (TNFB 1/2). Both TNFA2 and TNFB2 alleles are associated w ith high TNF-alpha production in vitro and susceptibility to inflammat ory diseases. Given the importance of TNF-alpha in the pathogenesis of CHF, we studied the prevalence of TNF gene polymorphisms in CHF patie nts and the correlation of genotypes to in vivo TNF-alpha levels. Meth ods and Results-TNFA and TNFB genotypes were determined by the polymer ase 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=1 39; TNFA1/2=0.84/0.16, TNFB1/2=0.32/0.68). In 211 patients with CHF, c irculating levels of TNF-alpha and the soluble receptors type I and ty pe 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 bet ween TNFA or TNFB genotypes and circulating levels of TNF-alpha or its soluble receptors in the CHF patients. Conclusions-Despite their asso ciation with other inflammatory diseases, neither TNFA nor TNFB polymo rphisms are related to the presence of CHF or the elevation of circula ting TNF-alpha. Thus, other factors may be more important in determini ng the circulating levels of TNF-alpha in CHF.