Susceptibility loci reported in genome-wide association studies are associated with Crohn's disease in Canadian children.
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).


OBJECTIVE
To investigate whether reported genes/loci were also associated with CD in Canadian children.


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.


CONCLUSIONS
The identified susceptibility genes/loci for adult-onset CD also confer risk for paediatric-onset CD.
Amre
D K
DK
Department of Pediatrics, University of Montreal, QC, Canada. devendra.amre@umontreal.ca <devendra.amre@umontreal.ca>
Mack
D R
DR
Morgan
K
K
Israel
D
D
Deslandres
C
C
Seidman
E G
EG
Lambrette
P
P
Costea
I
I
Krupoves
A
A
Fegury
H
H
Dong
J
J
Grimard
G
G
Levy
E
E
D000293:Adolescent; D017668:Age of Onset; D002170:Canada / Q000453:epidemiology; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003424:Crohn Disease / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D016678:Genome; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors