title: NOD2/CARD15 gene polymorphisms in Crohn's disease: a genotype-phenotype analysis in Danish and Portuguese patients and controls.
abstract: BACKGROUND
  A North-South gradient in Crohn's disease (CD) implying a higher incidence in northern Europe compared to southern Europe has been established.
  
  
  OBJECTIVE
  To investigate whether there is a difference between Denmark and Portugal in the frequency of CARD15 mutations in CD patients compared to a healthy background population and to compare genotype-phenotype relations in the two countries.
  
  
  METHODS
  58 Danish patients and 29 Portuguese patients with CD were matched for age, sex and disease behaviour at time of diagnosis and compared with 200 healthy Danish and Portuguese controls. Phenotypes were recorded at year of diagnosis, 3 years after diagnosis and at end of follow-up. Patients were genotyped for Arg702Trp, Gly908Arg and Leu1007InsC.
  
  
  RESULTS
  22% of the Danish patients vs. 9% of Danish controls compared to 21% of the Portuguese patients vs. 16% had at least one mutation. Mutation rates in Danish patients were significantly different (p=0.02) compared with Danish controls, no difference (p=0.51) was found between Portuguese patients and controls. However, a possible relationship between CD and presence of genetic mutations was found when comparing the two countries (p=0.03) using the Mantel-Haenszel test. No difference in evolution of phenotypes and the CARD15 status in CD was found during follow-up between the two matched populations. Ileal disease correlated to high occurrence of CARD15.
  
  
  CONCLUSIONS
  No North-South gradient regarding occurrence of CARD15 was revealed. Although a trend towards more mutations in the Portuguese controls was seen, a relationship between CD and CARD15 mutations was observed in both countries.
authors.affiliation: Department of Gastroenterology, Hvidovre University Hospital, Copenhagen, Denmark. ida@vind.to
authors.forename: Ida
authors.initials: I
authors.lastname: Vind
authors.forename: Ana
authors.initials: A
authors.lastname: Vieira
authors.forename: Lotte
authors.initials: L
authors.lastname: Hougs
authors.forename: Lourdes
authors.initials: L
authors.lastname: Tavares
authors.forename: Lene
authors.initials: L
authors.lastname: Riis
authors.forename: Paal Skytt
authors.initials: PS
authors.lastname: Andersen
authors.forename: Henning
authors.initials: H
authors.lastname: Locht
authors.forename: Joao
authors.initials: J
authors.lastname: Freitas
authors.forename: Estela
authors.initials: E
authors.lastname: Monteiro
authors.forename: Ib Jarle
authors.initials: IJ
authors.lastname: Christensen
authors.forename: Pia
authors.initials: P
authors.lastname: Munkholm
mesh_terms: D000328:Adult; D016009:Chi-Square Distribution; D003424:Crohn Disease / Q000453:epidemiology / Q000235:genetics*; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015994:Incidence; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011174:Portugal / Q000453:epidemiology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein