A founder haplotype of APOE-Sendai mutation associated with lipoprotein glomerulopathy
A founder haplotype of APOE-Sendai mutation associated with lipoprotein glomerulopathy
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DOI：
10.1038/jhg.2013.8
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发表时间：
2013-02
影响因子：
3.5
通讯作者：
K. Toyota;Taeko Hashimoto;D. Ogino;A. Matsunaga;M. Ito;I. Masakane;N. Degawa;Hiroshi Sato;Sayuri Shirai;K. Umetsu;G. Tamiya;Takao Saito;K. Hayasaka
中科院分区：
文献类型：
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作者：
K. Toyota;Taeko Hashimoto;D. Ogino;A. Matsunaga;M. Ito;I. Masakane;N. Degawa;Hiroshi Sato;Sayuri Shirai;K. Umetsu;G. Tamiya;Takao Saito;K. Hayasaka
脂蛋白肾病(LPG)是一种以肾小球内脂蛋白血栓、高脂蛋白血症和血清载脂蛋白E(APOE)显著升高为特征的遗传性疾病。超过12个APOE突变被确定为LPG的原因，APOE-仙台(Arg145Pro)突变在日本东部包括山形县的患者中频繁检测到。近年来，强化降脂药物的有效治疗已经确立，需要流行病学资料才能早期诊断。我们对9个无关LPG家系的13例患者的APOE-仙台单倍型结构进行了检测，发现所有APOE-仙台突变的单倍型是相同的，提示APOE-仙台突变可能是通过创始人效应在日本患者中常见的。我们还使用TaqMan方法研究了山形县2023名对照组和418名血液透析患者的APOE-仙台基因频率，但没有发现任何携带该突变的受试者，这表明即使在日本东部，APOE-仙台在普通人群中也是非常罕见的。由于LPG的外显性低，除APOE突变外，其他遗传和/或表观遗传因素也被认为参与了LPG的发病。这些患者没有共同的APOE等位基因单倍型，有些患者的APOE等位基因单倍型与无症状携带者相同。这些结果提示对应的APOE等位基因可能与LPG的发病无关。LPG的发病机制尚需进一步研究。
Lipoprotein glomerulopathy (LPG) is a hereditary disease characterized by lipoprotein thrombi in the glomerulus, hyperlipoproteinemia, and a marked increase in serum apolipoprotein E (APOE). More than 12 APOE mutations have been identified as causes of LPG, and APOE-Sendai (Arg145Pro) mutation was frequently detected in patients from the eastern part of Japan including Yamagata prefecture. Recently, effective therapy with intensive lipid-lowering agents was established, and epidemiologic data are required for early diagnosis. We determined the haplotype structure of APOE-Sendai in 13 patients from 9 unrelated families with LPG, and found that the haplotype of all APOE-Sendai mutations was identical, suggesting that APOE-Sendai mutation is common in Japanese patients probably through a founder effect. We also studied the gene frequency of APOE-Sendai in 2023 control subjects and 418 patients receiving hemodialysis in Yamagata prefecture using the TaqMan method, but did not identify any subjects carrying the mutation, indicating that it is very rare in the general population even in the eastern part of Japan. In addition to APOE mutation, other genetic and/or epigenetic factors are considered to be involved in the pathogenesis of LPG because of its low penetrance. The patients did not have a common haplotype of the counterpart APOE allele, and some patients had the same haplotype of the counterpart APOE allele as the asymptomatic carriers. These results suggest that the counterpart APOE allele is not likely associated with the onset of LPG. Further study is required to clarify the pathogenesis of LPG.