Effects of tumor necrosis factor gene polymorphisms on patients with congestive heart failure. VEST Investigators for TNF Genotype Analysis. Vesnarinone Survival Trial.
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.


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.
Kubota
T
T
Division of Cardiology, University of Pittsburgh Medical Center, PA 15213, USA.
McNamara
D M
DM
Wang
J J
JJ
Trost
M
M
McTiernan
C F
CF
Mann
D L
DL
Feldman
A M
AM
D000328:Adult; D016022:Case-Control Studies; D017931:DNA Primers; D004198:Disease Susceptibility; D005260:Female; D005838:Genotype; D006333:Heart Failure / Q000097:blood* / Q000235:genetics*; D006801:Humans; D008233:Lymphotoxin-alpha / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics* / Q000378:metabolism*
D017931:DNA Primers; D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha