Departments of Medicine II - Grosshadern, University of Munich, Munich, Germany and Clinic for Preventive Dentistry and Parodontology, University of Munich, Munich, Germany.
PLoS One. 2007 Sep 5;2(9):e819. doi: 10.1371/journal.pone.0000819.
The IL23R gene has been identified as a susceptibility gene for inflammatory bowel disease (IBD) in the North American population. The aim of our study was to test this association in a large German IBD cohort and to elucidate potential interactions with other IBD genes as well as phenotypic consequences of IL23R variants.
Genomic DNA from 2670 Caucasian individuals including 833 patients with Crohn's disease (CD), 456 patients with ulcerative colitis (UC), and 1381 healthy unrelated controls was analyzed for 10 IL23R SNPs. Genotyping included the NOD2 variants p.Arg702Trp, p.Gly908Arg, and p.Leu1007fsX1008 and polymorphisms in SLC22A4/OCTN1 (1672 C-->T) and SLC22A5/OCTN2 (-207 G-->C).
All IL23R gene variants analyzed displayed highly significant associations with CD. The strongest association was found for the SNP rs1004819 [P = 1.92x10(-11); OR 1.56; 95 % CI (1.37-1.78)]. 93.2% of the rs1004819 TT homozygous carriers as compared to 78% of CC wildtype carriers had ileal involvement [P = 0.004; OR 4.24; CI (1.46-12.34)]. The coding SNP rs11209026 (p.Arg381Gln) was protective for CD [P = 8.04x10(-8); OR 0.43; CI (0.31-0.59)]. Similar, but weaker associations were found in UC. There was no evidence for epistasis between the IL23R gene and the CD susceptibility genes CARD15 and SLC22A4/5.
IL23R is an IBD susceptibility gene, but has no epistatic interaction with CARD15 and SLC22A4/5. rs1004819 is the major IL23R variant associated with CD in the German population, while the p.Arg381Gln IL23R variant is a protective marker for CD and UC.
IL23R 基因已被确定为北美人种中炎症性肠病（IBD）的易感基因。我们的研究旨在检验这一关联在一个大型德国 IBD 队列中的作用，并阐明其与其他 IBD 基因的潜在相互作用以及 IL23R 变异的表型后果。
对包括 833 例克罗恩病（CD）患者、456 例溃疡性结肠炎（UC）患者和 1381 例健康无关对照在内的 2670 名高加索个体的基因组 DNA 进行了 10 个 IL23R SNPs 的分析。基因分型包括 NOD2 变异 p.Arg702Trp、p.Gly908Arg 和 p.Leu1007fsX1008，以及 SLC22A4/OCTN1（1672C>T）和 SLC22A5/OCTN2（-207G>C）多态性。
所有分析的 IL23R 基因变异均与 CD 呈显著相关性。最强的相关性是 SNP rs1004819 [P=1.92x10(-11)；OR 1.56；95%CI(1.37-1.78)]。与 CC 野生型携带者相比，rs1004819TT 纯合子携带者中有 93.2%的回肠受累[P=0.004；OR 4.24；CI(1.46-12.34)]。编码 SNP rs11209026（p.Arg381Gln）对 CD 有保护作用[P=8.04x10(-8)；OR 0.43；CI(0.31-0.59)]。在 UC 中也发现了类似但较弱的相关性。IL23R 基因与 CD 易感基因 CARD15 和 SLC22A4/5 之间没有证据表明存在上位性。
IL23R 是一种 IBD 易感基因，但与 CARD15 和 SLC22A4/5 没有上位性相互作用。rs1004819 是德国人群中与 CD 相关的主要 IL23R 变异，而 p.Arg381Gln IL23R 变异是 CD 和 UC 的保护性标志物。
