title: CARD15 mutation analysis in an Italian population: Leu1007fsinsC but neither Arg702Trp nor Gly908Arg mutations are associated with Crohn's disease.
abstract: BACKGROUND
  CARD15 gene mutations have been demonstrated to confer a high risk of Crohn's disease (CD). Despite this, recent studies reported variable associations between CD and CARD15 mutations in distinct ethnic groups, thus raising the hypothesis that genetic and/or allelic heterogeneity may influence the relationship between CARD15 and CD. The purpose of this study was to evaluate the frequency of the main mutations of the CARD15 gene (Leu 1007fsinsC, Arg702Trp, and Gly908Arg) in Italian CD patients and to establish possible genotype-phenotype correlations.
  
  
  METHODS
  One hundred sixty-five CD patients and 125 healthy subjects were consecutively enrolled from January to November 2001. The Leu1007fsinsC mutation was assessed by denaturing high-performance liquid chromatography and Arg702Trp and Gly908Arg mutations by Pyrosequencing technology.
  
  
  RESULTS
  Among the CARD15 gene mutations tested, only the Leu1007fsinsC was associated with CD (30/165 CD patients, 18%, versus 3/125 healthy subjects, 2.4%; p < 0.001). In particular, 23 CD patients were heterozygotes and 7 were homozygotes. No healthy subject exhibited the mutant homozygous genotype. Odds ratios for CD were 6.9 for heterozygotes and 41.0 for homozygotes. The genotype-phenotype analysis revealed that a fibrostenosing CD of the distal ileum was more frequent in patients carrying the Leu1007fsinsC mutation.
  
  
  CONCLUSIONS
  This study confirms the association between CARD15 gene mutations and CD and shows that only the Leu1007fsinsC mutation is a risk factor of CD in an Italian population.
authors.affiliation: Cattedra di Gastroenterologia, Centro d'eccellenza per lo studio del rischio genomico in patologie complesse e multifattoriali, Università Tor Vergata, Rome, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Vavassori
authors.forename: Paola
authors.initials: P
authors.lastname: Borgiani
authors.forename: Livia
authors.initials: L
authors.lastname: Biancone
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: D'Apice
authors.forename: Giovanna Del Vecchio
authors.initials: Gdel V
authors.lastname: Blanco
authors.forename: Laura
authors.initials: L
authors.lastname: Vallo
authors.forename: Francesca
authors.initials: F
authors.lastname: De Nigris
authors.forename: Ivan
authors.initials: I
authors.lastname: Monteleone
authors.forename: Giovanni
authors.initials: G
authors.lastname: Monteleone
authors.forename: Francesco
authors.initials: F
authors.lastname: Pallone
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Novelli
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D016001:Confidence Intervals; D003424:Crohn Disease / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D006801:Humans; D015994:Incidence; D047908:Intracellular Signaling Peptides and Proteins; D007558:Italy / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011336:Probability; D012016:Reference Values; D018570:Risk Assessment; D017678:Sex Distribution; D018709:Statistics, Nonparametric
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein