Klein W, Tromm A, Griga T, Fricke H, Folwaczny C, Hocke M, Eitner K, Marx M, Duerig N, Epplen J T
Abteilung fuer Molekulare Humangenetik, Ruhr-Universitaet, Bochum, Germany.
Genes Immun. 2002 Dec;3(8):494-6. doi: 10.1038/sj.gene.6363897.
Inflammatory bowel diseases (IBD) are multifactorial disorders characterised by the host's inability to limit the inflammatory response to luminal antigens. The association of polymorphisms in the CARD15 gene with Crohn's disease (CD) demonstrates the relevance of activated transcription factor NF(kappa)B in mononuclear cells. Interleukin 11 (IL11) mediates anti-inflammatory effects and is able to downregulate LPS-induced NF(kappa)B activation. The IL11 gene is therefore a good candidate involved in genetic predisposition to IBD. To evaluate the role of the IL11 gene in IBD, two polymorphisms, including a dinucleotide repeat in the promoter region, have been genotyped in 222 patients with CD, 152 patients with ulcerative colitis (UC) and 400 healthy controls. PCR-SSCP analysis of the coding region revealed a single polymorphism in exon 4 leading to an amino acid exchange (G335A; R112H), not significantly associated with either disease. Dinucleotide repeat frequencies of the IL11.A1 allele and of IL11.A1 homozygous individuals were significantly increased among the patients with UC (P < 0.002 and (P < 0.003, respectively) but not with CD. Altered expression of IL11 appears to be involved in the genetic predisposition of UC.
炎症性肠病（IBD）是多因素疾病，其特征在于宿主无法限制对腔内抗原的炎症反应。CARD15基因多态性与克罗恩病（CD）的关联表明了活化转录因子NF（κ）B在单核细胞中的相关性。白细胞介素11（IL11）介导抗炎作用，并能够下调脂多糖诱导的NF（κ）B活化。因此，IL11基因是参与IBD遗传易感性的一个很好的候选基因。为了评估IL11基因在IBD中的作用，对222例CD患者、152例溃疡性结肠炎（UC）患者和400名健康对照者进行了两种多态性的基因分型，其中包括启动子区域的二核苷酸重复序列。编码区的PCR-SSCP分析显示外显子4中有一个单一多态性，导致氨基酸交换（G335A；R112H），与两种疾病均无显著相关性。IL11.A1等位基因和IL11.A1纯合个体的二核苷酸重复频率在UC患者中显著增加（分别为P < 0.002和P < 0.003），但在CD患者中未增加。IL11表达的改变似乎参与了UC的遗传易感性。
