TNF-α-308A promoter polymorphism is associated with enhanced TNF-α production and inflammatory activity in Crohn's patients with fistulizing disease

被引:122
作者
González, S
Rodrigo, L
Martínez-Borra, J
López-Vázquez, A
Fuentes, D
Niño, P
Cadahía, V
Saro, C
Dieguez, MA
López-Larrea, C
机构
[1] Hosp Cent Asturias, Dept Immunol, Oviedo 33006, Spain
[2] Hosp Cent Asturias, Dept Gastroenterol, Oviedo 33006, Spain
[3] Univ Oviedo, Dept Funct Biol, Oviedo, Spain
[4] Hosp Cabuenes, Dept Gastroenterol, Gijon, Spain
关键词
D O I
10.1016/S0002-9270(03)00134-5
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
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. (C) 2003 by Am. Coll. of Gastroenterology.
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页码:1101 / 1106
页数:6
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