Genetic analysis of the complement factor H related 5 gene in haemolytic uraemic syndrome
Genetic analysis of the complement factor H related 5 gene in haemolytic uraemic syndrome
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DOI：
10.1016/j.molimm.2006.08.004
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发表时间：
2007-03-01
影响因子：
3.6
通讯作者：
Noris, M.
中科院分区：
文献类型：
--
作者：
Monteferrante, G.;Brioschi, S.;Noris, M.
CFH 基因中的几种突变已在非志贺毒素相关溶血性尿毒综合征（非 Stx-HUS）中得到描述，这是一种以溶血性贫血、血小板减少和急性肾衰竭为特征的罕见综合征。编码其他补体调节蛋白、膜辅因子蛋白 (CD46) 和补体因子 I (CFI) 的基因突变也参与了该疾病的发病机制。无论如何，这三个基因的突变占非 Stx-HUS 病例的比例不超过 50%。 人补体因子 H 相关 5 (CFHR5) 是最近鉴定的人补体因子 H (CFH) 家族成员，已被发现是具有不同原因的硬化病变的人肾脏中免疫沉积物的组成部分。 CFHR5 具有辅助因子活性，并且已被认为在肾小球补体调节中发挥作用。我们筛选了 CFHR5 基因是否存在可能与 HUS 病因相关的变异。对 45 名 HUS 患者和 80 名对照者进行了分析。总共，在 9/45 的 HUS 患者和 4/80 的对照中发现了 CFHR5 的 5 个遗传变异。统计分析表明 CFHR5 的等位基因变异主要与 HUS 相关。基于这些数据，我们得出结论，CFHR5 基因改变虽然不是致病因素，但可能在 HUS 的发病机制中发挥次要作用。 (c) 2006 Elsevier Ltd. 保留所有权利。
Several mutations in the CFH gene have been described in non-Shiga-toxin-associated haemolytic uraemic syndrome (non-Stx-HUS), a rare syndrome characterized by haemolytic anaemia, thrombocytopenia and acute renal failure. Mutations in genes encoding other complement regulatory proteins, membrane cofactor protein (CD46) and complement factor I (CFI), were also involved in the pathogenesis of the disease. Anyway, mutations in the three genes account for no more than 50% of cases of non-Stx-HUS.Human complement factor H related 5 (CFHR5) is a recently characterised member of the human complement factor H (CFH) family that has been found as a component of immune deposits in human kidney with sclerotic lesions from different causes. CFHR5 possesses cofactor activity and has been proposed to play a role in complement regulation in the glomerulus.We screened CFHR5 gene for variations potentially involved in the aetiology of HUS. Forty-five patients with HUS and 80 controls were analysed. Altogether, 5 genetic variants in CFHR5 were found in overall 9/45 HUS patients and in 4/80 controls. Statistical analysis showed that allelic variants in CFHR5 were prefentially associated with HUS. Based on these data, we conclude that, though not causative, CFHR5 genetic alterations may play a secondary role in the pathogenesis of HUS. (c) 2006 Elsevier Ltd. All rights reserved.