Department of Pediatrics, University of Montreal, QC, Canada.
Aliment Pharmacol Ther. 2010 Jun;31(11):1186-91. doi: 10.1111/j.1365-2036.2010.04294.x. Epub 2010 Mar 8.
Recent genome-wide association studies based on adult and paediatric populations have implicated >30 genes/loci as susceptibility loci for Crohn's disease (CD).
To investigate whether reported genes/loci were also associated with CD in Canadian children.
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.
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.
The identified susceptibility genes/loci for adult-onset CD also confer risk for paediatric-onset CD.
基于成人和儿科人群的全基因组关联研究表明,超过 30 个基因/位点是克罗恩病(CD)的易感基因/位点。
研究加拿大儿童中报告的基因/位点是否也与 CD 相关。
在加拿大的三个儿科胃肠病学诊所实施了病例对照设计。招募了年龄<或=18 岁且确诊为 CD 的患儿作为病例,并招募了对照。对五个全基因组关联研究报告基因/位点的单核苷酸多态性(SNP)进行了基因分型。检查了个体 SNP 与 CD 之间的关联。
共研究了 406 例病例和 415 例对照。病例的平均(+/-标准差)年龄为 12.3(+/-3.2)岁。大多数病例为男性(56.6%),诊断时存在回肠结肠炎(L3 +/- L4,52.0%)和炎症性行为(B1 +/- p,86.9%)。等位基因关联分析(双侧)显示,五个靶向 SNP 中的三个与 CD 的总体易感性显著相关(ZNF365,r10995271,P=0.001;PTPN2,rs1893217,P=0.005;STAT3,rs744166,P=0.01)。PTGER4 基因座中的 SNP rs4613763 与 CD 的关联接近显著(P=0.07)。ZNF365 和 STAT3 SNP 主要与回肠疾病伴或不伴结肠受累相关。
成人发病 CD 的易感基因/位点也与儿科发病 CD 相关。