Bouma G, Peña A S
Academisch Ziekenhuis Vrije Universiteit, afd. Gastro-enterologie, Amsterdam.
Ned Tijdschr Geneeskd. 1999 Nov 27;143(48):2414-20.
Epidemiological and family studies have shown that the inflammatory bowel diseases (IBD), encompassing ulcerative colitis and Crohn's disease, are in large part genetically determined. This genetic susceptibility is complex and does not follow Mendelian inheritance patterns. The search for susceptibility genes is further complicated by genetic and clinical heterogeneity. Recent developments in molecular biology have enabled the identification of chromosomal regions and genes underlying IBD. Genetic association studies have established a role of HLA genes and cytokine gene polymorphisms in the pathogenesis of IBD. Whole genome linkage analysis studies using microsatellite markers and affected sib-pair analysis have identified two chromosomal locations (IBD1 on chromosome 16 and IBD2 on chromosome 12) associated with IBD. Recent investigations have shown that some chromosomal regions play a role in several autoimmune disorders. This suggests the presence of two types of genes in these diseases: genes that encode proteins that play a key role in the immune response and predisposing for autoimmune diseases in general, and disease-specific genes that are responsible for the phenotype and the severity of the disease.
流行病学和家族研究表明，包括溃疡性结肠炎和克罗恩病在内的炎症性肠病（IBD）在很大程度上由基因决定。这种遗传易感性很复杂，并不遵循孟德尔遗传模式。遗传和临床异质性使寻找易感基因的工作更加复杂。分子生物学的最新进展使得确定IBD相关的染色体区域和基因成为可能。遗传关联研究已证实HLA基因和细胞因子基因多态性在IBD发病机制中的作用。使用微卫星标记的全基因组连锁分析研究以及受累同胞对分析已确定了两个与IBD相关的染色体位置（16号染色体上的IBD1和12号染色体上的IBD2）。最近的研究表明，一些染色体区域在几种自身免疫性疾病中起作用。这表明这些疾病中存在两种类型的基因：编码在免疫反应中起关键作用且通常易患自身免疫性疾病的蛋白质的基因，以及负责疾病表型和严重程度的疾病特异性基因。
