Cinzia Ciccacci1, Cristina Politi1, Livia Biancone2, Andrea Latini1, Giuseppe Novelli1, Emma Calabrese2, Paola Borgiani3. 1. Department of Biomedicine and Prevention, Genetics Section, University of Rome "Tor Vergata", 00133, Rome, Italy. 2. Gastroenterology Unit, Department of Systems Medicine, University of Rome "Tor Vergata", Rome, Italy. 3. Department of Biomedicine and Prevention, Genetics Section, University of Rome "Tor Vergata", 00133, Rome, Italy. borgiani@med.uniroma2.it.
Abstract
BACKGROUND: Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC), are multifactorial disorders that result from a dysregulated inflammatory response to environmental factors in genetically predisposed individuals. Recently, microRNAs (miRNAs) have been shown to be involved in the development of IBDs. AIMS: We investigated common variants in five miRNA genes in a cohort of Italian IBD patients, to evaluate their possible role in the disease's susceptibility and phenotype manifestations. METHODS: The analysis included 267 CD patients, 207 UC patients, and 298 matched healthy controls. Polymorphisms in the MIR122, MIR499, MIR146A, MIR196A2, and MIR124A genes were evaluated by allelic discrimination assay. RESULTS: We did not find associations between mir polymorphisms and IBD susceptibility. In both diseases, rs17669 and rs11614913 (MIR122 and MIR196A2) seem to contribute to clinical phenotypes: ileal location in CD (odds ratio [OR] = 1.82, p = 0.03; OR = 0.51, p = 0.01), and left-sided extent in UC (OR = 0.43, p = 0.05; OR = 0.28, p = 0.002). In CD, the MIR124A polymorphism (rs531564) contributed to colon location (p = 0.03, OR = 2.74). Finally, the variant allele of rs11614913 was associated with early age at onset in both diseases (p = 0.05 and p = 0.02). CONCLUSIONS: We showed for the first time that polymorphisms in MIR122, MIR196A2, and MIR124A could play a role in clinical phenotype modulation in IBD.
BACKGROUND:Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC), are multifactorial disorders that result from a dysregulated inflammatory response to environmental factors in genetically predisposed individuals. Recently, microRNAs (miRNAs) have been shown to be involved in the development of IBDs. AIMS: We investigated common variants in five miRNA genes in a cohort of Italian IBD patients, to evaluate their possible role in the disease's susceptibility and phenotype manifestations. METHODS: The analysis included 267 CDpatients, 207 UC patients, and 298 matched healthy controls. Polymorphisms in the MIR122, MIR499, MIR146A, MIR196A2, and MIR124A genes were evaluated by allelic discrimination assay. RESULTS: We did not find associations between mir polymorphisms and IBD susceptibility. In both diseases, rs17669 and rs11614913 (MIR122 and MIR196A2) seem to contribute to clinical phenotypes: ileal location in CD (odds ratio [OR] = 1.82, p = 0.03; OR = 0.51, p = 0.01), and left-sided extent in UC (OR = 0.43, p = 0.05; OR = 0.28, p = 0.002). In CD, the MIR124A polymorphism (rs531564) contributed to colon location (p = 0.03, OR = 2.74). Finally, the variant allele of rs11614913 was associated with early age at onset in both diseases (p = 0.05 and p = 0.02). CONCLUSIONS: We showed for the first time that polymorphisms in MIR122, MIR196A2, and MIR124A could play a role in clinical phenotype modulation in IBD.
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