Abstract
AIM: We investigated the contribution of variants of tumour necrosis factor (TNF)-α 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 AND METHODS: 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-α 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-α 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-α 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.
| Original language | English |
|---|---|
| Pages (from-to) | 171-179 |
| Number of pages | 9 |
| Journal | Journal of Pediatric Gastroenterology and Nutrition |
| Volume | 44 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 2007 |
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Keywords
- 6-Mercaptopurine
- Azathioprine
- Corticosteroids
- Genotype/phenotype
- Infliximab
- Medical therapy
- Mesalamine
- Methotrexate
ASJC Scopus subject areas
- Gastroenterology
- Histology
- Medicine (miscellaneous)
- Food Science
- Pediatrics, Perinatology, and Child Health
Cite this
Polymorphisms of tumor necrosis factor-α but not MDR1 influence response to medical therapy in pediatric-onset inflammatory bowel disease. / Cucchiara, Salvatore; Latiano, Anna; Palmieri, Orazio; Canani, Roberto Berni; D'Inca, Renata; Guariso, Graziella; Vieni, Giuseppe; De Venuto, Domenica; Riegler, Gabriele; De'Angelis, Gian Luigi; Guagnozzi, Danila; Bascietto, Cinzia; Miele, Erasmo; Valvano, Maria Rosa; Bossa, Fabrizio; Annese, Vito.
In: Journal of Pediatric Gastroenterology and Nutrition, Vol. 44, No. 2, 02.2007, p. 171-179.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Polymorphisms of tumor necrosis factor-α but not MDR1 influence response to medical therapy in pediatric-onset inflammatory bowel disease
AU - Cucchiara, Salvatore
AU - Latiano, Anna
AU - Palmieri, Orazio
AU - Canani, Roberto Berni
AU - D'Inca, Renata
AU - Guariso, Graziella
AU - Vieni, Giuseppe
AU - De Venuto, Domenica
AU - Riegler, Gabriele
AU - De'Angelis, Gian Luigi
AU - Guagnozzi, Danila
AU - Bascietto, Cinzia
AU - Miele, Erasmo
AU - Valvano, Maria Rosa
AU - Bossa, Fabrizio
AU - Annese, Vito
PY - 2007/2
Y1 - 2007/2
N2 - AIM: We investigated the contribution of variants of tumour necrosis factor (TNF)-α 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 AND METHODS: 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-α 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-α 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-α 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.
AB - AIM: We investigated the contribution of variants of tumour necrosis factor (TNF)-α 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 AND METHODS: 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-α 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-α 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-α 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.
KW - 6-Mercaptopurine
KW - Azathioprine
KW - Corticosteroids
KW - Genotype/phenotype
KW - Infliximab
KW - Medical therapy
KW - Mesalamine
KW - Methotrexate
UR - http://www.scopus.com/inward/record.url?scp=33846644967&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846644967&partnerID=8YFLogxK
U2 - 10.1097/MPG.0b013e31802c41f3
DO - 10.1097/MPG.0b013e31802c41f3
M3 - Article
C2 - 17255827
AN - SCOPUS:33846644967
VL - 44
SP - 171
EP - 179
JO - Journal of Pediatric Gastroenterology and Nutrition
JF - Journal of Pediatric Gastroenterology and Nutrition
SN - 0277-2116
IS - 2
ER -