Polymorphisms of tumor necrosis factor-α but not MDR1 influence response to medical therapy in pediatric-onset inflammatory bowel disease

Salvatore Cucchiara, Anna Latiano, Orazio Palmieri, Roberto Berni Canani, Renata D'Inca, Graziella Guariso, Giuseppe Vieni, Domenica De Venuto, Gabriele Riegler, Gian Luigi De'Angelis, Danila Guagnozzi, Cinzia Bascietto, Erasmo Miele, Maria Rosa Valvano, Fabrizio Bossa, Vito Annese

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)171-179
Number of pages9
JournalJournal of Pediatric Gastroenterology and Nutrition
Volume44
Issue number2
DOIs
Publication statusPublished - Feb 2007

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Crohn disease
tumor necrosis factors
inflammatory bowel disease
colitis
Ulcerative Colitis
Inflammatory Bowel Diseases
Crohn Disease
odds ratio
Tumor Necrosis Factor-alpha
Odds Ratio
genetic polymorphism
Pediatrics
therapeutics
Genes
genes
resection
single nucleotide polymorphism
steroids
Single Nucleotide Polymorphism
Therapeutics

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 journalArticle

Cucchiara, S, Latiano, A, Palmieri, O, Canani, RB, D'Inca, R, Guariso, G, Vieni, G, De Venuto, D, Riegler, G, De'Angelis, GL, Guagnozzi, D, Bascietto, C, Miele, E, Valvano, MR, Bossa, F & Annese, V 2007, 'Polymorphisms of tumor necrosis factor-α but not MDR1 influence response to medical therapy in pediatric-onset inflammatory bowel disease', Journal of Pediatric Gastroenterology and Nutrition, vol. 44, no. 2, pp. 171-179. https://doi.org/10.1097/MPG.0b013e31802c41f3
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. / Polymorphisms of tumor necrosis factor-α but not MDR1 influence response to medical therapy in pediatric-onset inflammatory bowel disease. In: Journal of Pediatric Gastroenterology and Nutrition. 2007 ; Vol. 44, No. 2. pp. 171-179.
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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.",
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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

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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.

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KW - Corticosteroids

KW - Genotype/phenotype

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