Tsao B P, Cantor R M, Kalunian K C, Wallace D J, Hahn B H, Rotter J I
UCLA Department of Medicine, Division of Rheumatology 90095-1670, USA.
Proc Assoc Am Physicians. 1998 Mar-Apr;110(2):113-7.
Although cumulative evidence suggests that a genetic predisposition plays a major role in the development of systemic lupus erythematosus (SLE), the susceptibility genes are mostly unknown. The difficulty in identifying susceptibility genes is due in part to the inherent nature of this polygenic complex disease and the diverse genetic backgrounds of human populations. Murine SLE models that have homogenous genetic backgrounds are less complex for genetic dissection. Genome-wide linkage studies of murine SLE have mapped the position of a number of susceptibility loci. Recently, several of these major murine loci have been shown to link to different clinical and laboratory features of lupus-like phenotypes. In addition, evidence for additional genetic contributions via interaction between murine loci has been reported. In human SLE, many polymorphic genes (which have potential roles in SLE, as suggested by their known functions) have been associated with SLE or SLE subsets by population-based case-control or within-case studies. Because more compelling genetic evidence includes linkage analysis, our group has used the identified murine susceptibility loci as a guide and conducted linkage analysis of genetic markers located within a specific, possibly syntenic human chromosomal region. Evidence for linkage of a chromosome 1q41-42 region was observed in SLE-affected sibling pairs from multiple ethnic groups. This article summarizes recent developments and outlines possible future directions in delineating the genetic basis of SLE.
尽管越来越多的证据表明遗传易感性在系统性红斑狼疮（SLE）的发病过程中起主要作用，但大多数易感基因仍不明确。识别易感基因存在困难，部分原因在于这种多基因复杂疾病的内在特性以及人类群体多样的遗传背景。具有同质遗传背景的小鼠SLE模型在基因剖析方面没那么复杂。对小鼠SLE进行的全基因组连锁研究已确定了多个易感位点的位置。最近，已证明其中一些主要的小鼠位点与狼疮样表型的不同临床和实验室特征相关。此外，有报道称小鼠位点之间的相互作用对遗传有额外贡献。在人类SLE中，许多多态性基因（根据其已知功能推测可能在SLE中起作用）已通过基于人群的病例对照研究或病例内研究与SLE或SLE亚组相关联。由于更有说服力的遗传证据包括连锁分析，我们小组已以已确定的小鼠易感位点为指导，对位于特定的、可能是同线的人类染色体区域内的遗传标记进行连锁分析。在来自多个种族群体的受SLE影响的同胞对中观察到1q41 - 42染色体区域存在连锁证据。本文总结了近期的进展，并概述了在阐明SLE遗传基础方面可能的未来方向。
