Variants at the 3p21 locus influence susceptibility and phenotype both in adults and early-onset patients with inflammatory bowel disease

Anna Latiano, Orazio Palmieri, Giuseppe Corritore, Maria Rosa Valvano, Fabrizio Bossa, Salvatore Cucchiara, Massimo Castro, Gabriele Riegler, Domenica De Venuto, Renata D'Incà, Angelo Andriulli, Vito Annese

Research output: Contribution to journalArticle

Abstract

Background: To date, a number of high-profile studies have yielded over 50 inflammatory bowel disease (IBD) disease genes/loci. The polymorphisms rs9858542 (BSN) and rs3197999 (MST1), on 3p21 locus, have been found associated with susceptibility to IBD. We aimed to replicate these associations in adult and early-onset cohorts of IBD Italian patients, by analyzing also potential gene-gene interactions with variants in NOD2/CARD15, IL23R, ATG16L1, and IRGM genes, and investigating genotype-phenotype correlation. Methods: In all, 1808 patients with IBD, 855 with Crohn's disease (CD) and 953 with ulcerative colitis (UC), including 539 patients with their initial diagnosis rs9858542 2.5 × 10-7; Prs3197999 3.9 × 10-7), and UC (Prs9858542 = 3.1 × 10-4; P rs3197999 = 8 × 10-4). Prevalence of these variants was significantly increased in both adult and earlyonset IBD patients. After stepwise logistic regression, the 2 variants were associated in adult UC with distal colitis (Prs9858542 = 0.013, odds ratio [OR] = 2.04, 95% confidence interval [CI] = 1.16-3.59; Prs3197999 = 0.018, OR 1.9, 95% CI 1.2-3.3), while the rs3197999 variant was inversely associated with occurrence of extraintestinal manifestations in adult CD(P = 0.017, OR 0.6, 95% CI 0.4-0.9). Conclusions: We confirmed the association of BSN and MST1 with IBD susceptibility, either in the adult or the early-onset cohorts. These variants appeared to influence either the distal location of the disease in the UC cohort and extraintestinal manifestations in CD patients.

Original languageEnglish
Pages (from-to)1108-1117
Number of pages10
JournalInflammatory Bowel Diseases
Volume16
Issue number7
DOIs
Publication statusPublished - 2010

Fingerprint

Inflammatory Bowel Diseases
Phenotype
Ulcerative Colitis
Crohn Disease
Odds Ratio
Confidence Intervals
Genes
Disease Susceptibility
Genetic Association Studies
Colitis
Logistic Models

Keywords

  • BSN
  • Crohn's disease
  • Genotype/phenotype
  • MST1
  • Ulcerative colitis

ASJC Scopus subject areas

  • Gastroenterology
  • Immunology and Allergy

Cite this

Variants at the 3p21 locus influence susceptibility and phenotype both in adults and early-onset patients with inflammatory bowel disease. / Latiano, Anna; Palmieri, Orazio; Corritore, Giuseppe; Valvano, Maria Rosa; Bossa, Fabrizio; Cucchiara, Salvatore; Castro, Massimo; Riegler, Gabriele; De Venuto, Domenica; D'Incà, Renata; Andriulli, Angelo; Annese, Vito.

In: Inflammatory Bowel Diseases, Vol. 16, No. 7, 2010, p. 1108-1117.

Research output: Contribution to journalArticle

Latiano, Anna ; Palmieri, Orazio ; Corritore, Giuseppe ; Valvano, Maria Rosa ; Bossa, Fabrizio ; Cucchiara, Salvatore ; Castro, Massimo ; Riegler, Gabriele ; De Venuto, Domenica ; D'Incà, Renata ; Andriulli, Angelo ; Annese, Vito. / Variants at the 3p21 locus influence susceptibility and phenotype both in adults and early-onset patients with inflammatory bowel disease. In: Inflammatory Bowel Diseases. 2010 ; Vol. 16, No. 7. pp. 1108-1117.
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abstract = "Background: To date, a number of high-profile studies have yielded over 50 inflammatory bowel disease (IBD) disease genes/loci. The polymorphisms rs9858542 (BSN) and rs3197999 (MST1), on 3p21 locus, have been found associated with susceptibility to IBD. We aimed to replicate these associations in adult and early-onset cohorts of IBD Italian patients, by analyzing also potential gene-gene interactions with variants in NOD2/CARD15, IL23R, ATG16L1, and IRGM genes, and investigating genotype-phenotype correlation. Methods: In all, 1808 patients with IBD, 855 with Crohn's disease (CD) and 953 with ulcerative colitis (UC), including 539 patients with their initial diagnosis rs9858542 2.5 × 10-7; Prs3197999 3.9 × 10-7), and UC (Prs9858542 = 3.1 × 10-4; P rs3197999 = 8 × 10-4). Prevalence of these variants was significantly increased in both adult and earlyonset IBD patients. After stepwise logistic regression, the 2 variants were associated in adult UC with distal colitis (Prs9858542 = 0.013, odds ratio [OR] = 2.04, 95{\%} confidence interval [CI] = 1.16-3.59; Prs3197999 = 0.018, OR 1.9, 95{\%} CI 1.2-3.3), while the rs3197999 variant was inversely associated with occurrence of extraintestinal manifestations in adult CD(P = 0.017, OR 0.6, 95{\%} CI 0.4-0.9). Conclusions: We confirmed the association of BSN and MST1 with IBD susceptibility, either in the adult or the early-onset cohorts. These variants appeared to influence either the distal location of the disease in the UC cohort and extraintestinal manifestations in CD patients.",
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T1 - Variants at the 3p21 locus influence susceptibility and phenotype both in adults and early-onset patients with inflammatory bowel disease

AU - Latiano, Anna

AU - Palmieri, Orazio

AU - Corritore, Giuseppe

AU - Valvano, Maria Rosa

AU - Bossa, Fabrizio

AU - Cucchiara, Salvatore

AU - Castro, Massimo

AU - Riegler, Gabriele

AU - De Venuto, Domenica

AU - D'Incà, Renata

AU - Andriulli, Angelo

AU - Annese, Vito

PY - 2010

Y1 - 2010

N2 - Background: To date, a number of high-profile studies have yielded over 50 inflammatory bowel disease (IBD) disease genes/loci. The polymorphisms rs9858542 (BSN) and rs3197999 (MST1), on 3p21 locus, have been found associated with susceptibility to IBD. We aimed to replicate these associations in adult and early-onset cohorts of IBD Italian patients, by analyzing also potential gene-gene interactions with variants in NOD2/CARD15, IL23R, ATG16L1, and IRGM genes, and investigating genotype-phenotype correlation. Methods: In all, 1808 patients with IBD, 855 with Crohn's disease (CD) and 953 with ulcerative colitis (UC), including 539 patients with their initial diagnosis rs9858542 2.5 × 10-7; Prs3197999 3.9 × 10-7), and UC (Prs9858542 = 3.1 × 10-4; P rs3197999 = 8 × 10-4). Prevalence of these variants was significantly increased in both adult and earlyonset IBD patients. After stepwise logistic regression, the 2 variants were associated in adult UC with distal colitis (Prs9858542 = 0.013, odds ratio [OR] = 2.04, 95% confidence interval [CI] = 1.16-3.59; Prs3197999 = 0.018, OR 1.9, 95% CI 1.2-3.3), while the rs3197999 variant was inversely associated with occurrence of extraintestinal manifestations in adult CD(P = 0.017, OR 0.6, 95% CI 0.4-0.9). Conclusions: We confirmed the association of BSN and MST1 with IBD susceptibility, either in the adult or the early-onset cohorts. These variants appeared to influence either the distal location of the disease in the UC cohort and extraintestinal manifestations in CD patients.

AB - Background: To date, a number of high-profile studies have yielded over 50 inflammatory bowel disease (IBD) disease genes/loci. The polymorphisms rs9858542 (BSN) and rs3197999 (MST1), on 3p21 locus, have been found associated with susceptibility to IBD. We aimed to replicate these associations in adult and early-onset cohorts of IBD Italian patients, by analyzing also potential gene-gene interactions with variants in NOD2/CARD15, IL23R, ATG16L1, and IRGM genes, and investigating genotype-phenotype correlation. Methods: In all, 1808 patients with IBD, 855 with Crohn's disease (CD) and 953 with ulcerative colitis (UC), including 539 patients with their initial diagnosis rs9858542 2.5 × 10-7; Prs3197999 3.9 × 10-7), and UC (Prs9858542 = 3.1 × 10-4; P rs3197999 = 8 × 10-4). Prevalence of these variants was significantly increased in both adult and earlyonset IBD patients. After stepwise logistic regression, the 2 variants were associated in adult UC with distal colitis (Prs9858542 = 0.013, odds ratio [OR] = 2.04, 95% confidence interval [CI] = 1.16-3.59; Prs3197999 = 0.018, OR 1.9, 95% CI 1.2-3.3), while the rs3197999 variant was inversely associated with occurrence of extraintestinal manifestations in adult CD(P = 0.017, OR 0.6, 95% CI 0.4-0.9). Conclusions: We confirmed the association of BSN and MST1 with IBD susceptibility, either in the adult or the early-onset cohorts. These variants appeared to influence either the distal location of the disease in the UC cohort and extraintestinal manifestations in CD patients.

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