Dubinsky Marla C, Wang Dai, Picornell Yoana, Wrobel Iwona, Katzir Lirona, Quiros Antonio, Dutridge Debra, Wahbeh Ghassan, Silber Gary, Bahar Ron, Mengesha Emebet, Targan Stephan R, Taylor Kent D, Rotter Jerome I
Department of Pediatrics, Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Inflamm Bowel Dis. 2007 May;13(5):511-5. doi: 10.1002/ibd.20126.
The IL-23 receptor (IL-23R) has been found to be associated with small bowel Crohn's disease (CD) in a whole genome association study. Specifically, the rare allele of the R381Q single nucleotide polymorphism (SNP) conferred protection against CD. It is unknown whether IL-23R is associated with IBD in children. The aim was to examine the association of IL-23R with susceptibility to IBD in pediatric patients.
DNA was collected from 609 subjects (151 CD and 52 ulcerative colitis [UC] trios). Trios were genotyped for the R381Q SNP of the IL-23R gene and SNP8, SNP12, SNP13, of the CARD15 gene using Taqman. The transmission disequilibrium test (TDT) was used for association to disease using GENEHUNTER 2.0.
The rare allele of R381Q SNP was present in 2.7% of CD and 2.9% UC probands. The CARD15 frequency was 31.5% (CD) and 18% (UC). The IL-23R allele was negatively associated with inflammatory bowel disease (IBD): the R381Q SNP was undertransmitted in children with IBD (8 transmitted [T] versus 27 untransmitted [UT]; P = 0.001). This association was significant for all CD patients (6 T versus 19 UT; P = 0.009), especially for non-Jewish CD patients (2 T versus 17 UT; P = 0.0006). TDT showed a borderline association for UC (2 T versus 8 UT; P = 0.06). As expected, CARD15 was associated with CD in children by the TDT (58 T versus 22 UT P = 0.00006), but not with UC.
The protective IL-23R R381Q variant was particularly associated with CD in non-Jewish children. Thus, the initial whole genome association study based on ileal CD in adults has been extended to the pediatric population and beyond small bowel CD.
在一项全基因组关联研究中发现，白细胞介素23受体（IL-23R）与小肠克罗恩病（CD）相关。具体而言，R381Q单核苷酸多态性（SNP）的罕见等位基因可预防CD。IL-23R是否与儿童炎症性肠病（IBD）相关尚不清楚。本研究旨在探讨IL-23R与儿科IBD易感性之间的关联。
收集了609名受试者（151例CD三联体和52例溃疡性结肠炎[UC]三联体）的DNA。使用Taqman对IL-23R基因的R381Q SNP以及CARD15基因的SNP8、SNP12、SNP13进行基因分型。使用GENEHUNTER 2.0软件的传递不平衡检验（TDT）分析疾病相关性。
R381Q SNP的罕见等位基因在2.7%的CD先证者和2.9%的UC先证者中出现。CARD15基因频率在CD患者中为31.5%，在UC患者中为18%。IL-23R等位基因与炎症性肠病（IBD）呈负相关：R381Q SNP在IBD儿童中传递不足（传递[T]8例，未传递[UT]27例；P = 0.001）。这种关联在所有CD患者中均有统计学意义（6 T vs 19 UT；P = 0.009），尤其是在非犹太裔CD患者中（2 T vs 17 UT；P = 0.0006）。TDT显示UC存在临界关联（2 T vs 8 UT；P = 0.06）。正如预期的那样，TDT显示CARD15基因与儿童CD相关（58 T vs 22 UT，P = 0.00006），但与UC无关。
具有保护作用的IL-23R R381Q变异体与非犹太裔儿童的CD尤其相关。因此，最初基于成人回肠CD的全基因组关联研究已扩展至儿科人群及小肠CD以外的疾病。
