Yang H, Rotter J I
Division of Medical Genetics, Steven Spielberg Pediatric Research Center, Burns and Allen Cedars-Sinai Research Institute, Los Angeles, USA.
Hepatogastroenterology. 2000 Jan-Feb;47(31):5-14.
Available evidence indicates that genetic factors are essential in providing the susceptibility to the majority of the various forms of inflammatory bowel disease occurring in man. It is also clear that the genetic susceptibility to these diseases is complex, and that more than one gene may predispose (the concept of multilocus/oligogenic inheritance), and likely in different etiologic combinations (the concept of genetic heterogeneity). Paradigms are now available that should lead to the identification of a number of these predisposing genes. These paradigms include the candidate gene approach, systematic genome wide scans, and mouse human synteny. While genome wide scans are currently limited to multiplex family linkage studies, both candidate genes and mouse human synteny can be approached in either linkage or association paradigms. Eventually whole genome association studies will be available as well. Identification of inflammatory bowel disease predisposing genes should lead to their incorporation in studies of natural history, investigation of environmental risk factors, and especially utilization of genetic markers in clinical trials. This will allow us to identify the best therapy available for the individual patient based on their unique genetic constitution. With advances in molecular technology, the search for genes influencing traits and diseases with a complex genetic background, such as the inflammatory bowel diseases, has become a realistic task. Although exogenous or infectious agents may contribute to the pathogenesis or may trigger the onset of disease, and the immune system almost certainly mediates the tissue damage, it is clear from available data that genetic factors determine the susceptibility of a given individual to inflammatory bowel disease (reviewed below). Thus, genetic studies are essential for the delineation of the basic etiologies of the various forms of inflammatory bowel disease and thus can aid in the development of radically new and specific therapies. In this review, we will discuss the importance and complexity of genetic factors in inflammatory bowel disease, methods and problems in the genetic dissection of complex traits, and future directions of genetic studies in inflammatory bowel disease.
现有证据表明，遗传因素对于人类发生的大多数各种形式的炎症性肠病的易感性至关重要。同样清楚的是，对这些疾病的遗传易感性很复杂，可能不止一个基因会导致易感性（多基因座/寡基因遗传的概念），并且可能存在于不同的病因组合中（遗传异质性的概念）。现在有一些范例有望导致识别出许多这些易感基因。这些范例包括候选基因方法、全基因组系统扫描以及小鼠与人的同线性。虽然目前全基因组扫描仅限于多重家系连锁研究，但候选基因和小鼠与人的同线性都可以通过连锁或关联范例来研究。最终全基因组关联研究也将可行。识别炎症性肠病的易感基因应会使其被纳入自然史研究、环境风险因素调查，尤其是在临床试验中利用遗传标记。这将使我们能够根据个体独特的基因构成确定最适合该患者的治疗方法。随着分子技术的进步，寻找影响具有复杂遗传背景的性状和疾病（如炎症性肠病）的基因已成为一项切实可行的任务。尽管外源性或感染性因素可能促成发病机制或引发疾病发作，并且免疫系统几乎肯定介导了组织损伤，但从现有数据可以清楚地看出，遗传因素决定了特定个体对炎症性肠病的易感性（如下文所述）。因此，遗传研究对于阐明各种形式的炎症性肠病的基本病因至关重要，从而有助于开发全新的特异性疗法。在本综述中，我们将讨论遗传因素在炎症性肠病中的重要性和复杂性、复杂性状遗传剖析的方法和问题，以及炎症性肠病遗传研究的未来方向。
