Analysis of polymorphisms affecting immune complex handling in systemic lupus erythematosus.
Analysis of polymorphisms affecting immune complex handling in systemic lupus erythematosus.
复制标题
影响系统性红斑狼疮免疫复合物处理的多态性分析。
DOI：
10.1093/rheumatology/keg157
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Petri,M
中科院分区：
文献类型：
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作者：
Sullivan,KE;Jawad,AF;Piliero,LM;Kim,N;Luan,X;Goldman,D;Petri,M
目标.系统性红斑狼疮（SLE）是一种炎症失调的多基因疾病。许多特定的候选基因已被确定，大多数涉及处理免疫复合物或抗原呈递。这与受影响终末器官中免疫复合物沉积的经典发现一致。我们希望研究参与免疫复合物清除的基因的多态性变体在狼疮易感性中的组合效应。本研究检测了基因多态性的发生，这些基因编码已知参与免疫复合物处理和清除的蛋白质。已知补体蛋白（C2、甘露糖结合蛋白和C4）、补体受体（CR 1）或Fc受体（Fc γ RIIA和Fc γ RIIIA）基因的每种多态性变体都会对功能产生不利影响。采用聚合酶链反应方法对160例SLE患者和212例对照者进行基因分型。我们发现SLE与越来越多的基因缺陷有着越来越大的关联。Fc γ RIIA和Fc γ RIIIA严重缺陷的组合对非裔美国人和高加索人患者特别有害，即使只有一种缺陷变体与SLE个体统计学显著相关。研究结果表明，基因可能以协同作用或改变单一遗传效应的方式相互作用，这意味着必须在种群的遗传背景下解释关联研究。
Objectives. Systemic lupus erythematosus (SLE) is a polygenic disorder of dysregulated inflammation. Numerous specific candidate genes have been identified and most relate to the handling of immune complexes or antigen presentation. This is consistent with the classic finding of immune complex deposition in affected end organs. We wished to examine combinatorial effects of polymorphic variants of genes involved in immune complex clearance in susceptibility to lupus.Methods. This study examined the occurrence of polymorphisms in genes which encode proteins known to be involved in immune complex handling and clearance. Each polymorphic variant of a complement protein (C2, mannose binding protein and C4), complement receptor (CR1) or Fc receptor (FcΓRIIA and FcΓRIIIA) gene is known to affect function adversely. One hundred and sixty SLE patients and 212 control subjects were genotyped using polymerase chain reaction methods.Results. We found an increasing association of SLE with increasing numbers of gene defects. Combinations of severe defects in FcΓRIIA and FcΓRIIIA were particularly deleterious for both African American and Caucasian patients, even though only one defective variant was individually statistically significantly associated with SLE.Conclusions. The results of the study suggest that genes may interact in ways that either synergize or modify the effect of a single genetic effect and imply that association studies must be interpreted within the genetic background of the populations.