Polymorphism at the C-reactive protein locus influences gene expression and predisposes to systemic lupus erythematosus.
Polymorphism at the C-reactive protein locus influences gene expression and predisposes to systemic lupus erythematosus.
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DOI：
10.1093/hmg/ddh021
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发表时间：
2004-01-01
影响因子：
3.5
通讯作者：
Vyse TJ
中科院分区：
文献类型：
--
作者：
Russell AI;Cunninghame Graham DS;Shepherd C;Roberton CA;Whittaker J;Meeks J;Powell RJ;Isenberg DA;Walport MJ;Vyse TJ
正五聚蛋白的相对缺乏与系统性红斑狼疮的发病机制有关。C-反应蛋白（CRP）反应在疾病急性发作的患者中是有缺陷的，并且血清淀粉样蛋白P组分基因（Sap）靶向缺失的小鼠发展为狼疮样疾病。在人类中，CRP（CRP）和SAP（APCS）的基因在与SLE相关的间隔内映射到1q23.2。我们调查了两个队列共586英国单SLE家庭的候选基因CRP和APCS。应用基于家族的关联和连锁试验，研究CRP和APCS基因中内含子二核苷酸重复序列和7个单核苷酸多态性的遗传。CRP基础水平独立地受CRP基因座的两个多态性影响，CRP 2和CRP 4。此外，后者的多态性与SLE和抗核自身抗体的产生相关。因此，与基础CRP降低相关的多态性也与SLE的发生相关。这些数据支持这一假设，即潜在的免疫原性材料的处理缺陷是狼疮发病机制的一个促成因素。确定基础CRP水平的多态性的鉴定在缺血性心脏病中具有意义，其中CRP水平是重要的风险预测因子。
Relative deficiency of pentraxin proteins is implicated in the pathogenesis of systemic lupus erythematosus. The C-reactive protein (CRP) response is defective in patients with acute flares of disease, and mice with targeted deletions of the serum amyloid P component gene (Sap) develop a lupus-like illness. In humans, the genes for CRP (CRP) and SAP (APCS) map to 1q23.2 within an interval linked with SLE. We have investigated the candidate genes CRP and APCS in two cohorts totalling 586 UK simplex SLE families. The inheritance of an intronic dinucleotide repeat and seven single nucleotide polymorphisms in the CRP and APCS genes was examined by application of family-based tests of association and linkage. Basal levels of CRP were influenced independently by two polymorphisms at the CRP locus, CRP 2 and CRP 4. Furthermore, the latter polymorphism was linked/associated with SLE and antinuclear autoantibody production. Thus, the polymorphism associated with reduced basal CRP was also associated with the development of SLE. These data support the hypothesis that defective disposal of potentially immunogenic material is a contributory factor in lupus pathogenesis. The identification of polymorphisms that determine basal CRP levels has implications in ischaemic heart disease, where CRP level is an important predictor of risk.