PMID- 12809834
OWN - NLM
STAT- MEDLINE
DCOM- 20030724
LR  - 20240109
IS  - 0002-9270 (Print)
IS  - 0002-9270 (Linking)
VI  - 98
IP  - 5
DP  - 2003 May
TI  - TNF-alpha -308A promoter polymorphism is associated with enhanced TNF-alpha 
      production and inflammatory activity in Crohn's patients with fistulizing 
      disease.
PG  - 1101-6
AB  - OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) plays a key role in the 
      inflammatory response and pathogenesis of Crohn's disease (CD). TNF-alpha -308A 
      polymorphism within the TNF-alpha gene promoter has been associated with enhanced 
      TNF-alpha production in vitro. The aim of this study was to investigate the 
      effect of TNF-alpha promoter polymorphism at -308 on the susceptibility and 
      phenotypic expression of fistulizing CD. METHODS: The distribution of -308 
      TNF-alpha genotypes was analyzed in 50 patients with fistulizing CD and 100 
      healthy matched controls. TNF-alpha, interleukin-1beta, and interleukin-6 serum 
      levels were measured by ELISA. Serum amyloid-A, C-reactive protein, 
      alpha1-antitrypsin, alpha1-acid glycoprotein, and haptoglobin were measured by 
      nephelometry. RESULTS: No significant differences were found in the allele 
      frequencies of the polymorphism between patients and controls. However, compared 
      with -308GG patients, those carrying -308AG had a significant increase of serum 
      levels of TNF-alpha (58 +/- 79 vs 8 +/- 19 pg/ml, p < 0.001), interleukin-1beta 
      (36 +/- 45 vs 16 +/- 20 pg/ml, p = 0.048), and acute phase proteins (APPs). -308A 
      carriers had also a higher frequency of arthritis (66% vs 26%, p = 0.039). The 
      logistic regression model showed that the patients carrying -308A polymorphism 
      had a relative risk for developing arthritis of 5.45 (95% CI = 1.1-25.6). No 
      other clinical or analytical findings were predictive for the risk of development 
      of arthritis. CONCLUSIONS: TNF-alpha -308A polymorphism is associated with 
      enhanced TNF-alpha production, more intense inflammatory activity, and an 
      increased risk for arthritis susceptibility in CD patients with fistulizing 
      disease.
FAU - Gonzalez, Segundo
AU  - Gonzalez S
AD  - Department of Functional Biology, University of Oviedo, Oviedo, Spain.
FAU - Rodrigo, Luis
AU  - Rodrigo L
FAU - Martinez-Borra, Jesus
AU  - Martinez-Borra J
FAU - Lopez-Vazquez, Antonio
AU  - Lopez-Vazquez A
FAU - Fuentes, Dolores
AU  - Fuentes D
FAU - Nino, Pilar
AU  - Nino P
FAU - Cadahia, Valle
AU  - Cadahia V
FAU - Saro, Cristina
AU  - Saro C
FAU - Dieguez, M Angeles
AU  - Dieguez MA
FAU - Lopez-Larrea, Carlos
AU  - Lopez-Larrea C
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Am J Gastroenterol
JT  - The American journal of gastroenterology
JID - 0421030
RN  - 0 (Acute-Phase Proteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Acute-Phase Proteins/analysis
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Case-Control Studies
MH  - Crohn Disease/*genetics/metabolism
MH  - Cutaneous Fistula/*genetics/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - Humans
MH  - Logistic Models
MH  - Male
MH  - Middle Aged
MH  - *Polymorphism, Genetic
MH  - Promoter Regions, Genetic
MH  - Rectal Fistula/*genetics/metabolism
MH  - Tumor Necrosis Factor-alpha/*biosynthesis/*genetics
EDAT- 2003/06/18 05:00
MHDA- 2003/07/25 05:00
CRDT- 2003/06/18 05:00
PHST- 2003/06/18 05:00 [pubmed]
PHST- 2003/07/25 05:00 [medline]
PHST- 2003/06/18 05:00 [entrez]
AID - S0002927003001345 [pii]
AID - 10.1111/j.1572-0241.2003.07416.x [doi]
PST - ppublish
SO  - Am J Gastroenterol. 2003 May;98(5):1101-6. doi: 10.1111/j.1572-0241.2003.07416.x.