ABSTRACT
BACKGROUND: Recent genome-wide association studies based on adult and paediatric populations have implicated >30 genes/loci as susceptibility loci for Crohn's disease (CD). AIMS: To investigate whether reported genes/loci were also associated with CD in Canadian children. DESIGN AND METHODS: A case-control design was implemented at three paediatric gastroenterology clinics in Canada. Children < or =18 years of age with a confirmed diagnosis of CD were recruited along with controls. Single nucleotide polymorphisms (SNPs) in five genome-wide association studies reported genes/loci were genotyped. Associations between individual SNPs and CD were examined. RESULTS: A total of 406 cases and 415 controls were studied. The mean (+/-s.d.) age of the cases was 12.3 (+/-3.2) years. Most cases were male (56.6%), had ileo-colonic disease (L3 +/- L4, 52.0%) and inflammatory behaviour (B1 +/- p, 86.9%) at diagnosis. Allelic association analysis (two-tailed) showed that three of the five targeted SNPs were significantly associated with overall susceptibility for CD (ZNF365, r10995271, P = 0.001; PTPN2, rs1893217, P = 0.005; STAT3, rs744166, P = 0.01). Associations with SNP rs4613763 in the PTGER4 locus were marginally nonsignificant (P = 0.07). The ZNF365 and STAT3 SNPs were predominantly associated with ileal disease with or without colonic involvement. CONCLUSION: The identified susceptibility genes/loci for adult-onset CD also confer risk for paediatric-onset CD.
Subject(s)
Crohn Disease/genetics , Genetic Loci/genetics , Genetic Predisposition to Disease , Adolescent , Age of Onset , Canada/epidemiology , Case-Control Studies , Child , Child, Preschool , Crohn Disease/epidemiology , Female , Genetic Predisposition to Disease/epidemiology , Genome , Genome-Wide Association Study , Genotype , Humans , Male , Polymorphism, Single Nucleotide , Risk FactorsABSTRACT
BACKGROUND: A recent genome-wide association study in adult patients with ulcerative colitis (UC) has implicated the interleukin 10 (IL-10) gene as an important candidate gene. Moreover, a UC-associated single nucleotide polymorphism (SNP) rs3024405 was also significantly associated with adult Crohn's disease (CD). AIMS: To examine whether IL-10-CD associations extended to paediatric-onset CD. METHODS: We implemented the case-control design at three paediatric gastroenterology clinics in Canada. CD patients (Subject(s)
Crohn Disease/genetics
, Haplotypes/genetics
, Interleukin-10/genetics
, Polymorphism, Single Nucleotide/genetics
, Adolescent
, Age of Onset
, Canada/epidemiology
, Case-Control Studies
, Child
, Child, Preschool
, Crohn Disease/epidemiology
, Female
, Gene Frequency
, Humans
, Male
, Reproducibility of Results
, Risk Factors
, Young Adult
