TY  - EJOU
AU  - Schulz, Susanne 
AU  - Schagdarsurengin, Undraga 
AU  - Suss, Thomas 
AU  - Müller-Werdan, Ursula 
AU  - Werdan, Karl 
AU  - Gläser, Christiane 

TI  - 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
T2  - European Cytokine Network

PY  - 2004
VL  - 15
IS  - 2
SN  - 1952-4005

AB  - 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).
KW  - TNF-α
KW  -  mRNA level
KW  -  protein level
KW  -  genetic background
KW  -  clinical and biochemical parameters

DO  -