Zheng Chang-Qing, Hu Gang-Zheng, Zeng Zhao-Shu, Lin Lian-Jie, Gu Gin-Ge
Department of Gastroenterology, the Second Affiliated Clinical College of China Medical University, Shenyang 110001, Liaoning Province, China.
World J Gastroenterol. 2003 Aug;9(8):1646-56. doi: 10.3748/wjg.v9.i8.1646.
Inflammatory bowel disease (IBD) includes two clinical subtypes: Crohn disease (CD) and ulcerative colitis (UC). The general prevalence is about 1.0-2.0 % in Western countries. It is predominantly regarded as a multifactorial disorder involving environmental factors and polygenic defects. The view was confirmed by a lot of evidences from clinical attributions and animal models, especially from epidemiological investigations. So the etiological study of IBD has been focused on searching for susceptibility genes by positional cloning, which consists of two steps: linkage analysis and association analysis. Linkage analysis has been an important method of searching for susceptibility genes to polygenic diseases as well as single-gene disorders. IBD, as a polygenic disease, has been widely investigated by linkage analysis for susceptibility gene since 1996. The paper reviewed 38 articles, which covered almost all original researches in relation to IBD and linkage analysis. So far, several loci, such as 16q, 12q, 6p and 3p, have been identified by the studies. The most striking is 16q12 (IBD1), which linked only with CD not UC in the majority of studies. Association analysis, as one essential step for positional cloning, is usually carried out by genotyping candidate genes selected by means of linkage analysis or other methods, for figuring out the frequencies of alleles and comparing the frequencies between IBD group and healthy control group to identify the specific allele. It has been established that IBD is implicated in immune disorder. So the studies were centered on the genes of NOD2/CARD15, HLA-II, cytokine, cytokine receptor and adhesion molecule. This paper reviewed 14 original articles on association between NOD2 and IBD that have been published since 2001. All results, with the exception of one report from a Japanese group, provide evidences that the three kinds of variants of NOD2 are susceptibility factors for IBD. This article also comprehensively analyzed 18 original researches of HLA gene polymorphism in IBD. We found extensive discrepancy among the conclusions and a novel hypothesis was put forward to explain the discordance. Most studies published recently on association between IBD and cytokine gene polymorphism were reviewed.
炎症性肠病（IBD）包括两种临床亚型：克罗恩病（CD）和溃疡性结肠炎（UC）。在西方国家，其总体患病率约为1.0%-2.0%。它主要被视为一种涉及环境因素和多基因缺陷的多因素疾病。这一观点已被来自临床归因、动物模型尤其是流行病学调查的大量证据所证实。因此，IBD的病因学研究一直聚焦于通过定位克隆寻找易感基因，这包括两个步骤：连锁分析和关联分析。连锁分析一直是寻找多基因疾病以及单基因疾病易感基因的重要方法。IBD作为一种多基因疾病，自1996年以来已通过连锁分析对其易感基因进行了广泛研究。本文回顾了38篇文章，这些文章几乎涵盖了所有与IBD和连锁分析相关的原始研究。到目前为止，通过这些研究已确定了几个基因座，如16q、12q、6p和3p。最引人注目的是16q12（IBD1），在大多数研究中它仅与CD相关，而与UC无关。关联分析作为定位克隆的一个关键步骤，通常通过对通过连锁分析或其他方法选择的候选基因进行基因分型来进行，以确定等位基因频率，并比较IBD组和健康对照组之间的频率，从而识别特定的等位基因。已经确定IBD与免疫紊乱有关。因此，研究集中在NOD2/CARD15、HLA-II、细胞因子、细胞因子受体和黏附分子等基因上。本文回顾了自2001年以来发表的14篇关于NOD2与IBD关联的原始文章。除了一个日本研究小组的一份报告外，所有结果都提供了证据表明NOD2的三种变体是IBD的易感因素。本文还全面分析了18项关于IBD中HLA基因多态性的原始研究。我们发现结论之间存在广泛差异，并提出了一个新的假说来解释这种不一致。本文还回顾了最近发表的大多数关于IBD与细胞因子基因多态性关联的研究。
