@Article{,
AUTHOR = {Susanne Schulz, Undraga Schagdarsurengin, Thomas Suss, Ursula Müller-Werdan, Karl Werdan, Christiane Gläser},
TITLE = {Relation between the <i>tumor necrosis factor</i>-α (TNF-α) gene and protein expression, and clinical, biochemical, and genetic markers: age, body mass index and uric acid are independent predictors for an elevated TNF-α plasma level in a complex risk model},
JOURNAL = {European Cytokine Network},
VOLUME = {15},
YEAR = {2004},
NUMBER = {2},
PAGES = {105--111},
URL = {http://www.techscience.com/ECN/v15n2/66387},
ISSN = {1952-4005},
ABSTRACT = {Background: Tumor necrosis factor-alpha (TNF-α) has been implicated in the pathogenesis of
numerous complex diseases. The plasma level of this pro-inflammatory cytokine is associated with a variety of
different risk factors, but little is known about the genetic background and the complex interactions. Methods: in
this clinical study, correlations were studied between plasma levels of circulating TNF-α protein (ELISA), its
mRNA expression in monocytes (RT-PCR) and genetic variants of TNF-α gene (SSCP), with several diseases,
including obesity, atherosclerosis, diabetes mellitus, hypertension, as well as risk factors such as age, gender,
inflammatory markers, the coagulation/fibrinolysis balance, and lipid metabolism. One hundred and ninety four
clinically and biochemically well-characterized patients were enrolled. Results: At the transcriptional level,
measured in monocytes, no association with any clinical or biochemical parameter investigated was found,
including TNF-α protein level. Investigating the influence of genetic variants of the TNF-α gene on mRNA and
protein levels, only one promoter polymorphism, namely c.-238G > A, was shown to be associated with
transcriptional but not with translational expression. However, at the translational level, significant positive, but
weak associations were determined for obesity (P = 0.037), age (P = 0.038), uric acid (P < 0.001), body mass index
(P = 0.01), plasminogen (P = 0.013), and fibrinogen (P = 0.002) in bivariate regression analyses, whereas HDL-cholesterol
(P = 0.005) was shown to be negatively correlated. However, investigating confounding effects in
stepwise multivariate regression analysis, body mass index (P = 0.009), uric acid (P = 0.026) and age (P = 0.037)
turned out to be significantly associated with plasma levels of circulating TNF-α (adjusted R<sup>2</sup> = 0.117; SE: 0.688).},
DOI = {}
}