Variants at the 3p21 locus influence susceptibility and phenotype both in adults and early-onset patients with inflammatory bowel disease
✍ Scribed by 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
- Book ID
- 102266266
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- English
- Weight
- 119 KB
- Volume
- 16
- Category
- Article
- ISSN
- 1078-0998
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✦ Synopsis
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 genotypephenotype 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 <19 years of age, and 651 controls were analyzed for SNPs rs9858542 and rs3197999.
Results: BSN and MST1 were significantly associated with either CD (P rs9858542 2.5 Â 10 À7 ; P rs3197999 3.9 Â 10 À7 ), and UC (P rs9858542 ¼ 3.1 Â 10 À4 ; P rs3197999 ¼ 8 Â 10 À4 ). 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 (P rs9858542 ¼ 0.013, odds ratio [OR] ¼ 2.04, 95% confidence interval [CI] ¼ 1.16-3.59; P rs3197999 ¼ 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 ¼ 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.