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.
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.
Authors: Devendra K Amre; David R Mack; Kenneth Morgan; David Israel; Colette Deslandres; Ernest G Seidman; Phlippe Lambrette; Irina Costea; Alfreda Krupoves; Houda Fegury; Jinsong Dong; Zia Xhu; Guy Grimard; Emile Levy Journal: Hum Genet Date: 2010-05-16 Impact factor: 4.132
Authors: Talin Haritunians; Michelle R Jones; Dermot P B McGovern; David Q Shih; Robert J Barrett; Carrie Derkowski; Marla C Dubinsky; Debra Dutridge; Phillip R Fleshner; Andrew Ippoliti; Lily King; Esther Leshinsky-Silver; Arie Levine; Gil Y Melmed; Emebet Mengesha; Eric A Vasilauskas; Shabnam Ziaee; Jerome I Rotter; Stephan R Targan; Kent D Taylor Journal: Gut Date: 2011-01-21 Impact factor: 23.059