Tomer Gitit, Ceballos Clare, Concepcion Erlinda, Benkov Keith J
Division of Pediatric Gastroenterology and Nutrition, The Children's Inflammatory Bowel Disease Center, Mount Sinai School of Medicine, New York, New York, USA.
Am J Gastroenterol. 2003 Nov;98(11):2479-84. doi: 10.1111/j.1572-0241.2003.08673.x.
NOD2/CARD15 variants have recently been shown to be associated with Crohn's disease (CD). No analysis of NOD2/CARD15 gene variants has so far been reported in pediatric patients. Therefore, our aim was to analyze NOD2/CARD15 gene variants in children with CD and to perform genotype-phenotype analyses.
We studied 101 children with CD and 136 healthy controls. Detailed phenotypic information was obtained from each patient. Patients were genotyped for the three NOD2/CARD15 variants R702W (single nucleotide polymorphism 8 [SNP8]), G908R (SNP12), and L1007fs (SNP13), and genotype-phenotype correlations were performed.
We found 33 NOD2/CARD15 mutations in 29 of 101 patients (29%). The frequency of NOD2 variation was 31% in white (n=87) compared with 11% in controls (chi2=14; p=0.0001; OR=3.7; 95% CI=1.7-7.8). Four white patients but not control subjects were compound heterozygotes. NOD2/CARD15 variants were significantly associated with ileal disease (chi2=4.5; p=0.03; OR=5; 95% CI=0.9-35.9). Of the children with NOD2/CARD15 variants, 44% were < or =5th percentile for weight at diagnosis, whereas only 15% of children without mutations were < or =5th percentile (chi2=8.7; p=0.003; OR=4.5; 95% CI=1.4-14.4). Similar trends were observed for height but they did not reach statistical significance.
Our results demonstrate that: 1) the three NOD2/CARD15 variants confer risk to CD in children; 2) NOD2/CARD15 variants are associated with ileal disease in children as in adults; and 3) NOD2/CARD15 variants are associated with lower weight percentiles at diagnosis in children and a tendency toward lower height percentile, suggesting an association between growth in children with CD.
最近研究显示NOD2/CARD15基因变异与克罗恩病（CD）相关。目前尚无关于儿科患者NOD2/CARD15基因变异的分析报道。因此，我们的目的是分析CD患儿的NOD2/CARD15基因变异并进行基因型-表型分析。
我们研究了101例CD患儿和136名健康对照者。从每位患者处获取详细的表型信息。对患者进行NOD2/CARD15的三种变异R702W（单核苷酸多态性8 [SNP8]）、G908R（SNP12）和L1007fs（SNP13）的基因分型，并进行基因型-表型相关性分析。
我们在101例患者中的29例（29%）发现了33个NOD2/CARD15突变。白人患者（n = 87）中NOD2变异的频率为31%，而对照组为11%（χ2 = 14；p = 0.0001；OR = 3.7；95% CI = 1.7 - 7.8）。4例白人患者而非对照者为复合杂合子。NOD2/CARD15变异与回肠疾病显著相关（χ2 = 4.5；p = 0.03；OR = 5；95% CI = 0.9 - 35.9）。在NOD2/CARD15变异的患儿中，44%在诊断时体重处于或低于第5百分位数，而无突变的患儿中只有15%处于或低于第5百分位数（χ2 = 8.7；p = 0.003；OR = 4.5；95% CI = 1.4 - 14.4）。身高方面观察到类似趋势，但未达到统计学显著性。
我们的结果表明：1）NOD2/CARD15的三种变异使儿童患CD的风险增加；2）NOD2/CARD15变异与儿童回肠疾病相关，如同在成人中一样；3）NOD2/CARD15变异与儿童诊断时较低的体重百分位数以及较低身高百分位数的趋势相关，提示与CD患儿的生长存在关联。
