Harley John B, Kelly Jennifer A
University of Oklahoma Health Sciences Center, Oklahoma City, USA.
J Natl Med Assoc. 2002 Aug;94(8):670-7.
Systemic lupus erythematosus (SLE) is a complex autoimmune disease involving critical genetic and environmental risk factors. SLE is a relatively common disease among African American women, affecting as many as one in 250. A collection of more than 250 African American and European American pedigrees multiplex for SLE have been collected in Oklahoma over the past decade for the purpose of identifying the genetic risk factors involved in the pathogenesis of SLE. A genome scan has been performed, and interestingly, the linkage results usually dominate in families from one or the other of these ethnicities. For example, the linkage effect at 1q21-22 near FcgammaRIIA is much stronger in the African American pedigrees than in the European American pedigrees. On the other hand, a gene near the top of chromosome4 (at 4p l6-15) contributes to SLE in the European American pedigrees, but not in the African American pedigrees. The racially-specific results lead to the tentative conclusion of genetic differences associated with SLE in African Americans and European Americans. The identification of the genes responsible for the observed linkage effects will provide fundamental knowledge concerning SLE and may even provide new targets for therapy and strategies to defeat this enigmatic and difficult disease.
系统性红斑狼疮(SLE)是一种复杂的自身免疫性疾病,涉及关键的遗传和环境风险因素。SLE在非裔美国女性中是一种相对常见的疾病,每250人中就有1人受影响。在过去十年中,俄克拉荷马州收集了250多个SLE多发的非裔美国人和欧裔美国人的家系,目的是确定参与SLE发病机制的遗传风险因素。已经进行了全基因组扫描,有趣的是,连锁结果通常在这些种族中的一个或另一个种族的家庭中占主导地位。例如,在1q21 - 22靠近FcγRIIA处的连锁效应在非裔美国家系中比在欧裔美国家系中要强得多。另一方面,4号染色体顶端附近(4p16 - 15)的一个基因在欧裔美国家系中对SLE有影响,但在非裔美国家系中没有。这种种族特异性结果导致初步结论,即非裔美国人和欧裔美国人中与SLE相关的遗传差异。确定导致观察到的连锁效应的基因将提供有关SLE的基础知识,甚至可能为治疗提供新靶点以及战胜这种神秘且难治疾病的策略。