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- Title
TNF-α −308A promoter polymorphism is associated with enhanced TNF-α production and inflammatory activity in Crohn’s patients with fistulizing disease
- Authors
González, Segundo; Rodrigo, Luis; Martínez-Borra, Jesús; López-Vázquez, Antonio; Fuentes, Dolores; Niño, Pilar; Cadahía, Valle; Saro, Cristina; Dieguez, M. Angeles; López-Larrea, Carlos
- Abstract
: ObjectiveTumor necrosis factor-α (TNF-α) plays a key role in the inflammatory response and pathogenesis of Crohn’s disease (CD). TNF-α −308A polymorphism within the TNF-α gene promoter has been associated with enhanced TNF-α production in vitro. The aim of this study was to investigate the effect of TNF-α promoter polymorphism at −308 on the susceptibility and phenotypic expression of fistulizing CD.: MethodsThe distribution of −308 TNF-α genotypes was analyzed in 50 patients with fistulizing CD and 100 healthy matched controls. TNF-α, interleukin-1β, and interleukin-6 serum levels were measured by ELISA. Serum amyloid-A, C-reactive protein, α1-antitrypsin, α1-acid glycoprotein, and haptoglobin were measured by nephelometry.: ResultsNo 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-α (58 ± 79 vs 8 ± 19 pg/ml, p < 0.001), interleukin-1β (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.: ConclusionsTNF-α −308A polymorphism is associated with enhanced TNF-α production, more intense inflammatory activity, and an increased risk for arthritis susceptibility in CD patients with fistulizing disease.
- Subjects
TUMOR necrosis factors; CROHN'S disease
- Publication
American Journal of Gastroenterology (Springer Nature), 2003, Vol 98, Issue 5, p1101
- ISSN
0002-9270
- Publication type
Article
- DOI
10.1016/S0002-9270(03)00134-5