title: A distinct pattern of disease-associated single nucleotide polymorphisms in IBD risk genes in a family with Crohn's disease.
abstract: Recent studies have identified more than 160 inflammatory bowel disease susceptibility loci and provided evidence for genetic heritability in disease pathogenesis. Here we describe a case of a 47-year-old White woman suffering from Crohn's disease (CD), who had four children, two with CD and two with a factor V Leiden variation. We analysed the presence of single nucleotide polymorphisms in several CD susceptibility genes. SNP analysis was carried out using commercially available assays. The female CD patient had a positive inflammatory bowel disease family history. All of the patients had a mild disease course, without fistulae or symptomatic stenosis. The patient was heterozygous for risk variants of the genes encoding nucleotide oligomerization domain 2 (NOD2) and Toll-like receptor 5 (TLR5) and a homozygous carrier of both of the identified protein tyrosine phosphatase nonreceptor type 2 (PTPN2) risk alleles. The CD-affected daughter carried heterozygous risk alleles of the genes encoding TLR5, NOD2 and PTPN2. The son, with the earliest onset of disease in the family at the age of 12 years, was heterozygous for risk alleles of autophagy 16 like 1 (ATG16L1), TLR5, NOD2 and PTPN2. This study reports an interesting pattern of CD-associated single nucleotide polymorphisms in a family with CD. This report clearly supports the observation that genetic variations, especially in genes associated with the innate immune system, contribute to disease onset.
authors.affiliation: aDivision of Gastroenterology and Hepatology, University Hospital Zurich bZurich Center for Integrative Human Physiology, University of Zurich, Zurich cDepartment of Internal Medicine, Kantonsspital Glarus, Glarus, Switzerland dDivision of Gastroenterology and Hepatology, Robert-Bosch-Hospital Stuttgart, Stuttgart, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Barthel
authors.forename: Marianne R
authors.initials: MR
authors.lastname: Spalinger
authors.forename: Jakob
authors.initials: J
authors.lastname: Brunner
authors.forename: Silvia
authors.initials: S
authors.lastname: Lang
authors.forename: Michael
authors.initials: M
authors.lastname: Fried
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rogler
authors.forename: Michael
authors.initials: M
authors.lastname: Scharl
mesh_terms: D000328:Adult; D002648:Child; D003424:Crohn Disease / Q000453:epidemiology / Q000235:genetics*; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2 / Q000235:genetics*; D012307:Risk Factors; D051198:Toll-Like Receptor 5 / Q000235:genetics*; D055815:Young Adult
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; C495346:TLR5 protein, human; D051198:Toll-Like Receptor 5; C516649:PTPN2 protein, human; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2