title: Transmission of CARD15 (NOD2) variants within families of patients with inflammatory bowel disease.
abstract: OBJECTIVE
  Three single nucleotide polymorphisms (SNPs) in CARD15 have been independently associated with Crohn's disease (CD). Since nothing is known about the transmission of these variants within families, this was the subject of our study in Flemish patients with inflammatory bowel disease (IBD) and their healthy relatives.
  
  
  METHODS
  A cohort of 1,670 individuals (570 CD, 173 UC, 165 healthy controls, 762 first-degree unaffected relatives of CD patients) was genotyped for Arg702Trp, Gly908Arg, and Leu1007fsinsC. Mutant allele and carrier frequencies were compared between groups. Segregation patterns were compared using a bivariate Dale model.
  
  
  RESULTS
  The carrier prevalence of CARD15 variants for CD patients was 46.3%, compared to 20.6% for healthy controls and 22.0% for ulcerative colitis (UC) patients (both p < 0.0001). An increased carriage rate of CARD15 variants was observed in unaffected relatives of CD patients (37.3%; p < 0.0001 vs controls), although this was significantly lower than in the CD patients (p = 0.001). Paternal transmission gave a 5.17-fold higher chance for the child to develop the disease compared to maternal transmission (95% CI [1.59, 16.78]; p = 0.0063). UC patients belonging to mixed IBD families carried significantly more mutations (42.3%) compared to other UC patients (18.4%) (p < 0.01).
  
  
  CONCLUSIONS
  Maternal transmission of the CARD15 variant allele is associated with a lower proportion of affected individuals compared to paternal transmission. Therefore, maternal transmission does not carry an increased risk of transmission as does paternal transmission. The increased mutation carriage in unaffected siblings of CD patients and in UC patients belonging to mixed families suggests that other factors than CARD15 contribute to the eventual disease expression.
authors.affiliation: Department of Gastroenterology, UZ Gasthuisberg, Leuven, Belgium.
authors.forename: Nele
authors.initials: N
authors.lastname: Esters
authors.forename: Marie
authors.initials: M
authors.lastname: Pierik
authors.forename: Kristel
authors.initials: K
authors.lastname: van Steen
authors.forename: Severine
authors.initials: S
authors.lastname: Vermeire
authors.forename: Greet
authors.initials: G
authors.lastname: Claessens
authors.forename: Sofie
authors.initials: S
authors.lastname: Joossens
authors.forename: Robert
authors.initials: R
authors.lastname: Vlietinck
authors.forename: Paul
authors.initials: P
authors.lastname: Rutgeerts
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001530:Belgium / Q000453:epidemiology; D002352:Carrier Proteins / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D015870:Gene Expression / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006579:Heterozygote; D006801:Humans; D007077:Ileal Diseases / Q000453:epidemiology / Q000235:genetics*; D015212:Inflammatory Bowel Diseases / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D040582:Inheritance Patterns; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D053473:Nod2 Signaling Adaptor Protein; D010641:Phenotype; D015995:Prevalence
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein