Differences between adults and children: genetics and

Clinical observations and epidemiological studies have highlighted some important differences in disease course and phenotypes between pediatric inflammatory bowel disease (IBD) and adult-onset IBD. Also from a therapeutic angle, the approach to young-onset IBD is different with a more rapid introduction of azathioprine and a high threshold for long and systemic steroid use, which may affect bone mineral density and growth. The observed clinical differences have been an area of scientific research and genetic studies have been the focus of attention. Specific candidate gene studies as well as genome-wide association studies have been performed in pediatric IBD. With the exception of very early-onset IBD occurring before the age of 2 years; no overt differences in genetic susceptibility have been identified. In contrast, very early-onset IBD seems in particular to be a genetic disease with defects in the IL10 signaling pathway being the principal example. This review aims to answer some straightforward questions arising in this topic by giving concise information.

[1]  Se Jin Song,et al.  The treatment-naive microbiome in new-onset Crohn's disease. , 2014, Cell host & microbe.

[2]  Jan Verhaegen,et al.  A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis , 2013, Gut.

[3]  C. Manichanh,et al.  Colonisation by Faecalibacterium prausnitzii and maintenance of clinical remission in patients with ulcerative colitis , 2013, Alimentary pharmacology & therapeutics.

[4]  L. Dauchet,et al.  Natural history of elderly-onset inflammatory bowel disease: a population-based cohort study , 2013, Gut.

[5]  M. Silverberg,et al.  IL-10R Polymorphisms Are Associated with Very-early-onset Ulcerative Colitis , 2013, Inflammatory bowel diseases.

[6]  R. Kellermayer Epigenetics and the developmental origins of inflammatory bowel diseases. , 2012, Canadian journal of gastroenterology = Journal canadien de gastroenterologie.

[7]  David C. Wilson,et al.  Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease , 2012, Nature.

[8]  J. Puchalka,et al.  Loss of interleukin-10 signaling and infantile inflammatory bowel disease: implications for diagnosis and therapy. , 2012, Gastroenterology.

[9]  M. Fraga,et al.  Epigenetics and the environment: emerging patterns and implications , 2012, Nature Reviews Genetics.

[10]  F. Rieux-Laucat,et al.  Defective IL10 Signaling Defining a Subgroup of Patients With Inflammatory Bowel Disease , 2011, The American Journal of Gastroenterology.

[11]  David P Bick,et al.  Making a definitive diagnosis: Successful clinical application of whole exome sequencing in a child with intractable inflammatory bowel disease , 2011, Genetics in Medicine.

[12]  P. Vandamme,et al.  Dysbiosis of the faecal microbiota in patients with Crohn's disease and their unaffected relatives , 2011, Gut.

[13]  Tariq Ahmad,et al.  Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci , 2010, Nature Genetics.

[14]  Dror Berel,et al.  Fucosyltransferase 2 (FUT2) non-secretor status is associated with Crohn's disease. , 2010, Human molecular genetics.

[15]  Kathryn Roeder,et al.  Genome-wide association identifies multiple ulcerative colitis susceptibility loci , 2010, Nature Genetics.

[16]  Christian Gieger,et al.  Genome-wide association study for ulcerative colitis identifies risk loci at 7q22 and 22q13 (IL17REL) , 2010, Nature Genetics.

[17]  Johan Van Limbergen,et al.  Common variants at five new loci associated with early-onset inflammatory bowel disease , 2009, Nature Genetics.

[18]  A. Schäffer,et al.  Inflammatory bowel disease and mutations affecting the interleukin-10 receptor. , 2009, The New England journal of medicine.

[19]  P. Donnelly,et al.  Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region , 2010 .

[20]  M. Daly,et al.  Established genetic risk factors do not distinguish early and later onset Crohn's disease , 2009, Inflammatory bowel diseases.

[21]  S. Cucchiara,et al.  The Microbiota in Inflammatory Bowel Disease in Different Age Groups , 2009, Digestive Diseases.

[22]  D. Strachan,et al.  Sequence variants in IL10, ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility , 2008, Nature Genetics.

[23]  J. Doré,et al.  Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients , 2008, Proceedings of the National Academy of Sciences.

[24]  Kathryn Roeder,et al.  Ulcerative colitis loci on chromosomes 1 p 36 and 12 q 15 identified by genome-wide association study , 2009 .

[25]  Julia Salleron,et al.  Natural history of pediatric Crohn's disease: a population-based cohort study. , 2008, Gastroenterology.

[26]  Joseph T. Glessner,et al.  Loci on 20q13 and 21q22 are associated with pediatric-onset inflammatory bowel disease , 2008, Nature Genetics.

[27]  David C Wilson,et al.  Definition of phenotypic characteristics of childhood-onset inflammatory bowel disease. , 2008, Gastroenterology.

[28]  S. Kugathasan,et al.  Genetic variants in the autophagy pathway contribute to paediatric Crohn’s disease , 2008, Gut.

[29]  Judy H. Cho,et al.  Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease , 2008, Nature Genetics.

[30]  M. Spehlmann,et al.  Epidemiology of inflammatory bowel disease in a German twin cohort: Results of a nationwide study , 2008, Inflammatory bowel diseases.

[31]  D. Hommes,et al.  Genetic susceptibility has a more important role in pediatric‐onset Crohn's disease than in adult‐onset Crohn's disease , 2007, Inflammatory bowel diseases.

[32]  A. Levine,et al.  Mucosal T-cell immunoregulation varies in early and late inflammatory bowel disease , 2007, Gut.

[33]  Alastair Forbes,et al.  Sequence variants in the autophagy gene IRGM and multiple other replicating loci contribute to Crohn's disease susceptibility , 2007, Nature Genetics.

[34]  Daniel B. DiGiulio,et al.  Development of the Human Infant Intestinal Microbiota , 2007, PLoS biology.

[35]  Judy H Cho,et al.  Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis , 2007, Nature Genetics.

[36]  S. Cucchiara,et al.  Gut-associated bacterial microbiota in paediatric patients with inflammatory bowel disease , 2006, Gut.

[37]  H. Freeman Age-Dependent Phenotypic Clinical Expression of Crohn's Disease , 2005, Journal of clinical gastroenterology.

[38]  H. Goto,et al.  Intestinal Fibroblast-Derived IL-10 Increases Survival of Mucosal T Cells by Inhibiting Growth Factor Deprivation- and Fas-Mediated Apoptosis 1 , 2005, The Journal of Immunology.

[39]  R. Sartor,et al.  Variable phenotypes of enterocolitis in interleukin 10-deficient mice monoassociated with two different commensal bacteria. , 2005, Gastroenterology.

[40]  M. Ray,et al.  Macrophage-Stimulating Protein, the Ligand for the Stem Cell-Derived Tyrosine Kinase/RON Receptor Tyrosine Kinase, Inhibits IL-12 Production by Primary Peritoneal Macrophages Stimulated with IFN-γ and Lipopolysaccharide1 , 2004, The Journal of Immunology.

[41]  Yun Hee Cho,et al.  In vivo inhibition of Fas ligand-mediated killing by TR6, a Fas ligand decoy receptor. , 2001, The Journal of pharmacology and experimental therapeutics.

[42]  Mourad Sahbatou,et al.  Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease , 2001, Nature.

[43]  Judy H. Cho,et al.  A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease , 2001, Nature.

[44]  R. Sartor,et al.  Resident Enteric Bacteria Are Necessary for Development of Spontaneous Colitis and Immune System Activation in Interleukin-10-Deficient Mice , 1998, Infection and Immunity.

[45]  Jean Weissenbach,et al.  Mapping of a susceptibility locus for Crohn's disease on chromosome 16 , 1996, Nature.

[46]  M. Silverberg,et al.  Gene-centric association mapping of chromosome 3p implicates MST1 in IBD pathogenesis , 2008, Mucosal Immunology.