Trucco M, Dorman J S
Department of Pediatrics, University of Pittsburgh, School of Medicine, Pennsylvania.
Crit Rev Immunol. 1989;9(3):201-45.
Diabetes mellitus is the second most prevalent chronic disease in children in the U.S. It is associated with severe manifestations which include blindness and circulation deficiencies as well as markedly increased risk of death. The etiology of diabetes mellitus remains a mystery although both genetic and environmental factors have been implicated. The geneticist is confronted with a number of obstacles in his attempts to unravel this problem, including differences in the definition of affected individuals. This matter was certainly clarified by the separation of noninsulin-dependent diabetes (NIDDM) and insulin-dependent diabetes mellitus (IDDM) into two separate disease entities. Twin studies, however, show that IDDM cannot be entirely due to genetic causes as concordance is no more than about 50%. Although the disease is then clearly not inherited per se, the "susceptibility" to diabetes seems almost surely inherited and, provided this susceptibility, the disease can be brought on by environmental factors. Until the underlying mechanism causing IDDM is completely ascertained, we have to rely on genetic markers to approach the study of the inheritance thereof. Since, in the early 1970s, research by Nerup's and Cudworth's groups revealed associations between the HLA-B locus and IDDM, the HLA markers are considered the classical genetic markers for IDDM susceptibility. In this paper, we review the nature of the genetic susceptibility to IDDM and the possible environmental factors which can bring on the disease.
糖尿病是美国儿童中第二常见的慢性疾病。它与严重的症状相关，包括失明和循环系统缺陷，以及死亡风险显著增加。尽管遗传因素和环境因素都被认为与糖尿病的病因有关，但糖尿病的病因仍然是个谜。遗传学家在试图解开这个问题时面临许多障碍，包括对受影响个体定义的差异。非胰岛素依赖型糖尿病（NIDDM）和胰岛素依赖型糖尿病（IDDM）被分为两个独立的疾病实体，这无疑澄清了这个问题。然而，双胞胎研究表明，IDDM不可能完全由遗传原因导致，因为其一致性不超过50%。虽然这种疾病本身显然不是遗传性的，但对糖尿病的“易感性”似乎几乎肯定是遗传的，并且在存在这种易感性的情况下，疾病可由环境因素引发。在导致IDDM的潜在机制完全确定之前，我们不得不依靠遗传标记来研究其遗传方式。自20世纪70年代初以来，内鲁普（Nerup）和库德沃思（Cudworth）团队的研究揭示了HLA - B基因座与IDDM之间的关联，HLA标记被认为是IDDM易感性的经典遗传标记。在本文中，我们综述了IDDM遗传易感性的本质以及可能引发该疾病的环境因素。
