Cucchiara S, Latiano A, Palmieri O, Staiano A M, D'Incà R, Guariso G, Vieni G, Rutigliano V, Borrelli O, Valvano M R, Annese V
Clinica Pediatrica, Università L Sapienza, Roma, Italy.
World J Gastroenterol. 2007 Feb 28;13(8):1221-9. doi: 10.3748/wjg.v13.i8.1221.
To investigate the contribution of variants of CARD15, OCTN1/2 and DLG5 genes in disease predisposition and phenotypes in a large Italian cohort of pediatric patients with inflammatory bowel diseases (IBD).
Two hundred patients with Crohn's disease (CD), 186 ulcerative colitis (UC) patients, 434 parents (217 trios), and 347 healthy controls (HC) were studied. Polymorphisms of the three major variants of CARD15, 1672C/T and -207G/C SNPs for OCTN genes, IGR2096a_1 and IGR2198a_1 SNPs for the IBD5 locus, and 113G/A variant of the DLG5 gene were evaluated. Potential correlations with clinical sub-phenotypes were investigated.
Polymorphisms of CARD15 were significantly associated with CD, and at least one variant was found in 38% of patients (15% in HC, OR = 2.7, P < 0.001). Homozygosis for both OCTN1/2 variants was more common in CD patients (1672TT 24%, -207CC 29%) than in HC (16% and 21%, respectively; P = 0.03), with an increased frequency of the TC haplotype (44.8% vs 38.3% in HC, P = 0.04). No association with the DLG5 variant was found. CD carriers of OCTN1/2 and DLG5 variants more frequently had penetrating disease (P = 0.04 and P = 0.01), while carriers of CARD15 more frequently had ileal localization (P = 0.03). No gene-gene interaction was found. In UC patients, the TC haplotype was more frequent (45.4%, P = 0.03), but no genotype/phenotype correlation was observed.
Polymorphisms of CARD15 and OCTN genes, but not DLG5 are associated with pediatric onset of CD. Polymorphisms of CARD15, OCTN, and DLG5 genes exert a weak influence on CD phenotype.
在一个大型意大利儿科炎症性肠病（IBD）队列中，研究CARD15、OCTN1/2和DLG5基因变异在疾病易感性和表型中的作用。
对200例克罗恩病（CD）患者、186例溃疡性结肠炎（UC）患者、434名父母（217个三联体）和347名健康对照（HC）进行研究。评估了CARD15的三个主要变异的多态性、OCTN基因的1672C/T和-207G/C单核苷酸多态性（SNP）、IBD5位点的IGR2096a_1和IGR2198a_1 SNP以及DLG5基因的113G/A变异。研究了与临床亚表型的潜在相关性。
CARD15多态性与CD显著相关，38%的患者中发现至少一种变异（HC中为15%，OR = 2.7，P < 0.001）。OCTN1/2两个变异的纯合子在CD患者中（1672TT为24%，-207CC为29%）比在HC中更常见（分别为16%和21%；P = 0.03），TC单倍型频率增加（HC中为38.3%，CD患者中为44.8%，P = 0.04）。未发现与DLG5变异相关。OCTN1/2和DLG5变异的CD携带者更常出现穿透性疾病（P = 0.04和P = 0.01），而CARD15携带者更常出现回肠定位（P = 0.03）。未发现基因-基因相互作用。在UC患者中，TC单倍型更常见（45.4%，P = 0.03），但未观察到基因型/表型相关性。
CARD15和OCTN基因的多态性而非DLG5与儿童期CD发病相关。CARD15、OCTN和DLG5基因的多态性对CD表型影响较弱。
