PMID- 15319168
OWN - NLM
STAT- MEDLINE
DCOM- 20050203
LR  - 20151119
IS  - 1148-5493 (Print)
IS  - 1148-5493 (Linking)
VI  - 15
IP  - 2
DP  - 2004 Apr-Jun
TI  - Relation between the tumor necrosis factor-alpha (TNF-alpha) gene and protein 
      expression, and clinical, biochemical, and genetic markers: age, body mass index 
      and uric acid are independent predictors for an elevated TNF-alpha plasma level 
      in a complex risk model.
PG  - 105-11
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) 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-alpha protein (ELISA), its mRNA expression in monocytes 
      (RT-PCR) and genetic variants of TNF-alpha 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-alpha 
      protein level. Investigating the influence of genetic variants of the TNF-alpha 
      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-alpha (adjusted R(2) -/+ 0.117; SE: 0.688).
FAU - Schulz, Susanne
AU  - Schulz S
AD  - Institute of Human Genetics and Medical Biology, Department of Medicine III, 
      Martin-Luther-Universitat Halle-Wittenberg.
FAU - Schagdarsurengin, Undraga
AU  - Schagdarsurengin U
FAU - Suss, Thomas
AU  - Suss T
FAU - Muller-Werdan, Ursula
AU  - Muller-Werdan U
FAU - Werdan, Karl
AU  - Werdan K
FAU - Glaser, Christiane
AU  - Glaser C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - France
TA  - Eur Cytokine Netw
JT  - European cytokine network
JID - 9100879
RN  - 0 (Biomarkers)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 268B43MJ25 (Uric Acid)
SB  - IM
MH  - Adult
MH  - Age Factors
MH  - Biomarkers/analysis
MH  - Blood Coagulation/genetics/physiology
MH  - Body Mass Index
MH  - Diabetes Mellitus/blood/*genetics
MH  - Female
MH  - Fibrinolysis/genetics/physiology
MH  - Gene Expression Regulation/genetics
MH  - *Genetic Predisposition to Disease
MH  - Humans
MH  - Hypertension/blood/*genetics
MH  - Male
MH  - Middle Aged
MH  - Monocytes/metabolism
MH  - Obesity/blood/*genetics
MH  - *Polymorphism, Single-Stranded Conformational
MH  - Risk Factors
MH  - Sex Factors
MH  - Tumor Necrosis Factor-alpha/analysis/*genetics
MH  - Uric Acid/blood
EDAT- 2004/08/21 05:00
MHDA- 2005/02/04 09:00
CRDT- 2004/08/21 05:00
PHST- 2004/08/21 05:00 [pubmed]
PHST- 2005/02/04 09:00 [medline]
PHST- 2004/08/21 05:00 [entrez]
PST - ppublish
SO  - Eur Cytokine Netw. 2004 Apr-Jun;15(2):105-11.