Progress in searching for susceptibility gene for inflammatory bowel disease by positional cloning.
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.
Zheng
Chang-Qing
CQ
Department of Gastroenterology, the Second Affiliated Clinical College of China Medical University, Shenyang 110001, Liaoning Province, China. zhengchangqing88@163.com
Hu
Gang-Zheng
GZ
Zeng
Zhao-Shu
ZS
Lin
Lian-Jie
LJ
Gu
Gin-Ge
GG
D002352:Carrier Proteins / Q000235:genetics; D002874:Chromosome Mapping; D003001:Cloning, Molecular / Q000379:methods; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein; D011110:Polymorphism, Genetic
D002352:Carrier Proteins; C103673:HFE protein, human; D000071020:Hemochromatosis Protein; D015395:Histocompatibility Antigens Class I; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein