Crohn's disease localization displays different predisposing genetic variants

Orazio Palmieri, Fabrizio Bossa, Maria Rosa Valvano, Giuseppe Corritore, Tiziana Latiano, Giuseppina Martino, Renata D'Incà, Salvatore Cucchiara, Maria Pastore, Mario D'Altilia, Daniela Scimeca, Giuseppe Biscaglia, Angelo Andriulli, Anna Latiano

Research output: Contribution to journalArticle

Abstract

Background: Crohn's disease (CD) is a pathologic condition with different clinical expressions that may reflect an interplay between genetics and environmental factors. Recently, it has been highlighted that three genetic markers, NOD2, MHC and MST1, were associated to distinct CD sites, supporting the concept that genetic variations may contribute to localize CD. Genetic markers, previously shown to be associated with inflammatory bowel disease (IBD), were tested in CD patients with the aim to better dissect the genetic relationship between ileal, ileocolonic and colonic CD and ascertain whether a different genetic background would support the three disease sites as independent entities. Methods: A panel of 29 SNPs of 19 IBD loci were analyzed by TaqMan SNP allelic discrimination method both evaluating their distinct contribute and analyzing all markers jointly. Results: Seven hundred and eight CD patients and 537 healthy controls were included in the study. Of the overall population of patients, 237 patients had an ileal involvement (L1), 171 a colonic localization (L2), and the 300 remaining an ileocolon location (L3). We confirmed the association for 23 of 29 variations (P < 0.05). Compared to healthy controls, 16 variations emerged as associated to an ileum disease, 7 with a colonic disease and 14 with an ileocolonic site (P < 0.05). Comparing ileum to colonic CD, 5 SNPs (17%) were differentially associated (P < 0.05). A genetic model score that aggregated the risks of 23 SNPs and their odds ratios (ORs), yielded an Area Under the Curve (AUC) of 0.70 for the overall CD patients. By analyzing each CD location, the AUC remained at the same level for the ileal and ileocolonic sites (0.73 and 0.72, respectively), but dropped to a 0,66 value in patients with colon localization. Conclusions: Our findings reaffirm the existence of at least three different subgroups of CD patients, with a genetic signature distinctive for the three main CD sites.

Original languageEnglish
Article numbere0168821
JournalPLoS One
Volume12
Issue number1
DOIs
Publication statusPublished - Jan 1 2017

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Crohn disease
Crohn Disease
Colonic Diseases
Single Nucleotide Polymorphism
inflammatory bowel disease
Genetic Markers
Ileum
ileum
Area Under Curve
genetic markers
Genetic Models
digestive system diseases
Inflammatory Bowel Diseases
odds ratio
genetic background
genetic relationships
colon
Colon
Odds Ratio

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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Crohn's disease localization displays different predisposing genetic variants. / Palmieri, Orazio; Bossa, Fabrizio; Valvano, Maria Rosa; Corritore, Giuseppe; Latiano, Tiziana; Martino, Giuseppina; D'Incà, Renata; Cucchiara, Salvatore; Pastore, Maria; D'Altilia, Mario; Scimeca, Daniela; Biscaglia, Giuseppe; Andriulli, Angelo; Latiano, Anna.

In: PLoS One, Vol. 12, No. 1, e0168821, 01.01.2017.

Research output: Contribution to journalArticle

Palmieri, O, Bossa, F, Valvano, MR, Corritore, G, Latiano, T, Martino, G, D'Incà, R, Cucchiara, S, Pastore, M, D'Altilia, M, Scimeca, D, Biscaglia, G, Andriulli, A & Latiano, A 2017, 'Crohn's disease localization displays different predisposing genetic variants', PLoS One, vol. 12, no. 1, e0168821. https://doi.org/10.1371/journal.pone.0168821
Palmieri, Orazio ; Bossa, Fabrizio ; Valvano, Maria Rosa ; Corritore, Giuseppe ; Latiano, Tiziana ; Martino, Giuseppina ; D'Incà, Renata ; Cucchiara, Salvatore ; Pastore, Maria ; D'Altilia, Mario ; Scimeca, Daniela ; Biscaglia, Giuseppe ; Andriulli, Angelo ; Latiano, Anna. / Crohn's disease localization displays different predisposing genetic variants. In: PLoS One. 2017 ; Vol. 12, No. 1.
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AU - Palmieri, Orazio

AU - Bossa, Fabrizio

AU - Valvano, Maria Rosa

AU - Corritore, Giuseppe

AU - Latiano, Tiziana

AU - Martino, Giuseppina

AU - D'Incà, Renata

AU - Cucchiara, Salvatore

AU - Pastore, Maria

AU - D'Altilia, Mario

AU - Scimeca, Daniela

AU - Biscaglia, Giuseppe

AU - Andriulli, Angelo

AU - Latiano, Anna

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N2 - Background: Crohn's disease (CD) is a pathologic condition with different clinical expressions that may reflect an interplay between genetics and environmental factors. Recently, it has been highlighted that three genetic markers, NOD2, MHC and MST1, were associated to distinct CD sites, supporting the concept that genetic variations may contribute to localize CD. Genetic markers, previously shown to be associated with inflammatory bowel disease (IBD), were tested in CD patients with the aim to better dissect the genetic relationship between ileal, ileocolonic and colonic CD and ascertain whether a different genetic background would support the three disease sites as independent entities. Methods: A panel of 29 SNPs of 19 IBD loci were analyzed by TaqMan SNP allelic discrimination method both evaluating their distinct contribute and analyzing all markers jointly. Results: Seven hundred and eight CD patients and 537 healthy controls were included in the study. Of the overall population of patients, 237 patients had an ileal involvement (L1), 171 a colonic localization (L2), and the 300 remaining an ileocolon location (L3). We confirmed the association for 23 of 29 variations (P < 0.05). Compared to healthy controls, 16 variations emerged as associated to an ileum disease, 7 with a colonic disease and 14 with an ileocolonic site (P < 0.05). Comparing ileum to colonic CD, 5 SNPs (17%) were differentially associated (P < 0.05). A genetic model score that aggregated the risks of 23 SNPs and their odds ratios (ORs), yielded an Area Under the Curve (AUC) of 0.70 for the overall CD patients. By analyzing each CD location, the AUC remained at the same level for the ileal and ileocolonic sites (0.73 and 0.72, respectively), but dropped to a 0,66 value in patients with colon localization. Conclusions: Our findings reaffirm the existence of at least three different subgroups of CD patients, with a genetic signature distinctive for the three main CD sites.

AB - Background: Crohn's disease (CD) is a pathologic condition with different clinical expressions that may reflect an interplay between genetics and environmental factors. Recently, it has been highlighted that three genetic markers, NOD2, MHC and MST1, were associated to distinct CD sites, supporting the concept that genetic variations may contribute to localize CD. Genetic markers, previously shown to be associated with inflammatory bowel disease (IBD), were tested in CD patients with the aim to better dissect the genetic relationship between ileal, ileocolonic and colonic CD and ascertain whether a different genetic background would support the three disease sites as independent entities. Methods: A panel of 29 SNPs of 19 IBD loci were analyzed by TaqMan SNP allelic discrimination method both evaluating their distinct contribute and analyzing all markers jointly. Results: Seven hundred and eight CD patients and 537 healthy controls were included in the study. Of the overall population of patients, 237 patients had an ileal involvement (L1), 171 a colonic localization (L2), and the 300 remaining an ileocolon location (L3). We confirmed the association for 23 of 29 variations (P < 0.05). Compared to healthy controls, 16 variations emerged as associated to an ileum disease, 7 with a colonic disease and 14 with an ileocolonic site (P < 0.05). Comparing ileum to colonic CD, 5 SNPs (17%) were differentially associated (P < 0.05). A genetic model score that aggregated the risks of 23 SNPs and their odds ratios (ORs), yielded an Area Under the Curve (AUC) of 0.70 for the overall CD patients. By analyzing each CD location, the AUC remained at the same level for the ileal and ileocolonic sites (0.73 and 0.72, respectively), but dropped to a 0,66 value in patients with colon localization. Conclusions: Our findings reaffirm the existence of at least three different subgroups of CD patients, with a genetic signature distinctive for the three main CD sites.

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