Polymorphisms of tumor necrosis factor-alpha but not MDR1 influence response to medical therapy in pediatric-onset inflammatory bowel disease.
J Pediatr Gastroenterol Nutr
; 44(2): 171-9, 2007 Feb.
Article
en En
| MEDLINE
| ID: mdl-17255827
ABSTRACT
AIM:
We investigated the contribution of variants of tumour necrosis factor (TNF)-alpha and MDR1 genes in the predisposition and response to medical therapy in a large pediatric cohort of patients with Crohn disease (CD) and ulcerative colitis (UC). PATIENTS ANDMETHODS:
In this study, 200 patients with CD, 186 patients with UC, 434 parents (217 trios), and 347 healthy unrelated controls were investigated. Single-nucleotide polymorphisms -G308A and -C857T of the TNF-alpha gene and C3435T of the MDR1 gene were investigated and correlated with clinical subphenotypes and efficacy of medical therapy.RESULTS:
The frequency of the -308A allele of the TNF-alpha gene was significantly increased in both patients with CD (15%; odds ratio [OR] = 2.79; P < 0.01) and patients with UC (11%; OR = 1.96; P < 0.003) compared with controls (6%). Carriers of this allele were 27% in CD (OR = 2.94; P < 0.01) and 19% in UC (OR = 1.86; P = 0.015) compared with 11% in healthy controls. No significant difference was found for both the -C857T and C3435T single-nucleotide polymorphisms. With the genotype/phenotype analysis, no correlation in patients with UC with the MDR1 gene was found. CD carriers of the -308A allele had a higher frequency of surgical resection (35% vs 20%; OR = 2.1; P = 0.035) and more frequent resistance to steroids (22% vs 8%; OR = 0.29; P = 0.032) compared with noncarriers. These findings were confirmed by stepwise logistic regression.CONCLUSIONS:
In our pediatric cohort, the promoter -308A polymorphism of TNF-alpha but not the MDR1 gene is significantly involved in the predisposition to both CD and UC. This polymorphism carries a significant reduction in response to steroid therapy, probably leading to a more frequent need for surgical resection.
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Bases de datos:
MEDLINE
Asunto principal:
Enfermedades Inflamatorias del Intestino
/
Factor de Necrosis Tumoral alfa
/
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP
/
Glucocorticoides
/
Inmunosupresores
Tipo de estudio:
Clinical_trials
Límite:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
J Pediatr Gastroenterol Nutr
Año:
2007
Tipo del documento:
Article
País de afiliación:
Italia