PMID- 17728075
OWN - NLM
STAT- MEDLINE
DCOM- 20080311
LR  - 20221207
IS  - 0376-8716 (Print)
IS  - 0376-8716 (Linking)
VI  - 92
IP  - 1-3
DP  - 2008 Jan 1
TI  - A study on the TNF-alpha system in Caucasian Spanish patients with alcoholic 
      liver disease.
PG  - 91-9
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) is thought to be a critical 
      driving force of inflammatory damage in alcoholic liver disease (ALD). We aimed 
      to establish whether there is a correlation between plasma levels of the soluble 
      TNF-alpha receptors 1 and 2 (sTNFR1 and sTNFR2) and the severity of liver damage 
      in patients with ALD. We also aimed to elucidate whether functionally active 
      polymorphisms in the promoter region of the TNF-alpha gene modulate the 
      development of ALD. DESIGN: We studied 614 Spaniards. Of these, 278 were 
      alcoholics (103 without liver histologic abnormalities, 89 with non-cirrhotic 
      liver disease and 86 with cirrhosis) and 336 were non-alcoholics (115 healthy 
      controls, 114 with non-alcoholic non-cirrhotic liver disease and 107 with 
      cirrhosis unrelated to alcohol). Plasma levels of sTNFR1 and sTNFR2 were 
      determined by ELISA and results were expressed in ng/mL and subsequently 
      converted in log(10). TNF-alpha gene promoter region polymorphisms at the 
      positions -238, -308 and -863 were assessed by restriction fragment length 
      polymorphisms (RFLPs) on white cell DNA. Differences in plasma sTNFR1 and sTNFR2 
      levels between groups were compared with the one-way and two-factor analysis of 
      variance test, and Student's t-test. Genotype distribution and allele frequencies 
      in the different groups were compared using the chi(2) test or Fisher's exact 
      test. RESULTS: sTNFR1 and sTNFR2 plasma levels were significantly higher in 
      patients with cirrhosis than in those with non-cirrhotic liver disease (p<0.001) 
      and individuals without liver disease (p<0.001), both in the alcoholic and the 
      non-alcoholic group. Among cirrhotics, sTNFR1 and sTNFR2 levels had a significant 
      positive correlation with the severity of the liver disease, graded with the 
      Child-Pugh's score (p=0.003 and p<0.001, respectively). TNF-alpha genotype 
      distribution and allele frequencies of the three loci assessed were similar in 
      the groups studied, hence no particular genotype or haplotype could be linked to 
      ALD. CONCLUSIONS: The TNF-alpha system is activated in patients with cirrhosis of 
      the liver irrespective of aetiology. TNF-alpha polymorphisms at positions -238, 
      -308 and -863 are not linked to ALD.
FAU - Auguet, Teresa
AU  - Auguet T
AD  - Hospital Universitari de Tarragona Joan XXIII, Tarragona, Spain; Universitat 
      Rovira i Virgili, Tarragona, Spain. tauguet.hj23.ics@gencat.net
FAU - Vidal, Francesc
AU  - Vidal F
FAU - Lopez-Dupla, Miguel
AU  - Lopez-Dupla M
FAU - Broch, Montserrat
AU  - Broch M
FAU - Gutierrez, Cristina
AU  - Gutierrez C
FAU - Olona, Montserrat
AU  - Olona M
FAU - Oltra, Carmina
AU  - Oltra C
FAU - Aguilar, Carmen
AU  - Aguilar C
FAU - Gonzalez, Eva
AU  - Gonzalez E
FAU - Quer, Joan-Carles
AU  - Quer JC
FAU - Sirvent, Joan-Josep
AU  - Sirvent JJ
FAU - Richart, Cristobal
AU  - Richart C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070828
PL  - Ireland
TA  - Drug Alcohol Depend
JT  - Drug and alcohol dependence
JID - 7513587
RN  - 0 (Receptors, Tumor Necrosis Factor, Type I)
RN  - 0 (Receptors, Tumor Necrosis Factor, Type II)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Aged
MH  - Alcohol Drinking/psychology
MH  - DNA/genetics
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Liver Diseases, Alcoholic/epidemiology/*genetics
MH  - Male
MH  - Middle Aged
MH  - Polymorphism, Restriction Fragment Length/genetics
MH  - Polymorphism, Single Nucleotide/genetics
MH  - Promoter Regions, Genetic/genetics
MH  - Prospective Studies
MH  - Receptors, Tumor Necrosis Factor, Type I/blood/genetics
MH  - Receptors, Tumor Necrosis Factor, Type II/blood/genetics
MH  - Spain/epidemiology
MH  - Tumor Necrosis Factor-alpha/*genetics
MH  - White People
EDAT- 2007/08/31 09:00
MHDA- 2008/03/12 09:00
CRDT- 2007/08/31 09:00
PHST- 2007/02/12 00:00 [received]
PHST- 2007/06/21 00:00 [revised]
PHST- 2007/07/01 00:00 [accepted]
PHST- 2007/08/31 09:00 [pubmed]
PHST- 2008/03/12 09:00 [medline]
PHST- 2007/08/31 09:00 [entrez]
AID - S0376-8716(07)00279-7 [pii]
AID - 10.1016/j.drugalcdep.2007.07.008 [doi]
PST - ppublish
SO  - Drug Alcohol Depend. 2008 Jan 1;92(1-3):91-9. doi: 
      10.1016/j.drugalcdep.2007.07.008. Epub 2007 Aug 28.