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首页> 外文期刊>World journal of gastroenterology : >IL-10 and TNF-alpha promoter haplotypes are associated with childhood Crohn's disease location.
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IL-10 and TNF-alpha promoter haplotypes are associated with childhood Crohn's disease location.

机译：IL-10和TNF-α启动子的单倍型与儿童克罗恩病的位置有关。

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AIM: To determine the distribution and frequencies of the genotypes and haplotypes of the genes encoding for the glucocorticoid receptor (GR), the tumor necrosis factor (TNF)-alpha and the interleukin (IL)-10 in childhood Crohn's disease (CD) and to assess the impact of the corresponding DNA variants on clinical and disease phenotypes. METHODS: Ten variants in GR, TNF-alpha and IL-10 were genotyped in 113 childhood CD cases and 95 healthy subjects, both of French-Canadian origin. RESULTS: For the GR polymorphisms (R23K and N363S) and IL-10 variants in the 5'flanking region (-1082 G > A, -819 T > C and -592 A > C), no difference was observed in allele and genotype frequencies between CD patients and controls. At the haplotype level, we found three IL-10 haplotypes previously described in Caucasians (GCC, ACC and ATA) and three novel haplotypes only present in IBD patients. When we analyzed the haplotype distribution with the anatomical location of the disease, the GCC haplotype was associated with the colonic and the ACC haplotype with the terminal ileum location, respectively. The genotyping of five polymorphisms in the promoter region of the TNF-alpha gene (-1031 T > C, -863 A > C, -857 T > C, -308 A > G and -238 A > G) revealed a significant overrepresentation of homozygous -1031 CC among CD patients (OR = 9.9) and an association with the colonic location. For TNF-alpha, eleven haplotypes were inferred, including two frequent ones, TCCGG and CACGG, which were significantly observed more frequently in controls and cases, respectively. CONCLUSION: This is one of the first studies investigating the association between haplotype structure and disease location in a CD pediatric cohort. Our results will help to increase our understanding of the genetic determinants of childhood CD.
机译：目的：确定儿童糖皮质激素受体（GR），肿瘤坏死因子（TNF）-α和白介素（IL）-10的编码基因的基因型和单倍型在儿童克罗恩病（CD）和评估相应DNA变体对临床和疾病表型的影响。方法：在113名儿童CD病例和95名健康受试者中，对10种GR，TNF-α和IL-10变异体进行了基因分型，均来自法国-加拿大血统。结果：对于5'侧翼区域（-1082 G> A，-819 T> C和-592 A> C）的GR多态性（R23K和N363S）和IL-10变异，在等位基因和基因型上没有发现差异CD患者和对照组之间的频率。在单倍型水平上，我们发现了先前在高加索人中描述的三种IL-10单倍型（GCC，ACC和ATA）和仅在IBD患者中存在的三种新型单倍型。当我们分析单倍型分布与疾病的解剖位置时，GCC单倍型与结肠相关，而ACC单倍型与回肠末端相关。 TNF-alpha基因启动子区域的五个多态性的基因分型（-1031 T> C，-863 A> C，-857 T> C，-308 A> G和-238 A> G）显示出明显的超表达CD患者中纯合子-1031 CC的分布（OR = 9.9），并与结肠位置有关。对于TNF-α，推断出11种单倍型，包括两种常见的单倍型，TCCGG和CACGG，分别在对照组和病例中更常见。结论：这是研究CD儿童队列中单倍型结构与疾病位置之间关系的第一批研究之一。我们的结果将有助于增进我们对儿童CD遗传决定因素的了解。

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