Mutations in the low-density lipoprotein receptor gene in Chinese familial hypercholesterolemia patients
Mutations in the low-density lipoprotein receptor gene in Chinese familial hypercholesterolemia patients
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DOI：
10.1161/01.atv.18.10.1600
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发表时间：
1998-10-01
影响因子：
8.7
通讯作者：
Masarei, JRL
中科院分区：
文献类型：
--
作者：
Mak, YT;Pang, CP;Masarei, JRL
据报道，在中国，杂合子家族性高胆固醇血症（FH）患者可能未被发现，因为他们没有黄色瘤或早发冠心病，而且他们的低密度脂蛋白胆固醇水平低于西方同行。然而，在香港的华人患者中，杂合子 FH 的表现似乎与西方国家或日本相似。我们研究了 30 名中国 FH 患者 LDL 受体基因 18 个外显子的启动子和编码区的序列变异。在 21 名患者中发现了 18 个突变，分布在启动子和 10 个外显子中。其中 11 个是本研究中首次发现的。我们还发现了 6 个等位基因频率与白人不同但与日本人相似的多态性，表明白人和东方人群之间存在一定的隔离。目前已知中国人的LDL受体基因共有29种突变。由于创始人效应，不存在明确的共同突变。同时，9例临床诊断的FH患者中未检测到LDL受体基因突变，其中载脂蛋白B的R3500Q突变也被排除。导致这些患者出现 EH 表型的基因缺陷可能发生在载脂蛋白 B 或其他相关基因的其他位置，甚至发生在 LDL 受体基因的非编码序列中。
It has been reported that in China, patients with heterozygous familial hypercholesterolemia (FH) may go unrecognized because they do not have xanthomata or premature coronary heart disease and their LDL cholesterol levels are lower than those in their Western counterparts. However, in the Chinese patients in Hong Kong, heterozygous FH appears to manifest in a way similar to that seen in Western countries or Japan. We studied sequence variations in the promoter and coding regions of the 18 exons of the LDL receptor gene in 30 Chinese FH patients. Eighteen mutations were identified in 21 patients scattered in the promoter and 10 exons. Eleven of them were first found in this study. We also found 6 polymorphisms with allelic frequencies different from those in whites but similar to the Japanese, indicating some isolation between white and Oriental populations. A total of 29 mutations in the LDL receptor gene are now known in the Chinese. There is no definite common mutation due to a founder effect. Meanwhile, there were no detectable LDL receptor gene mutations in 9 clinically diagnosed FH patients in whom the R3500Q mutation in apolipoprotein B had also been excluded. The gene defects leading to the EH phenotype in these patients may occur somewhere else in the apolipoprotein B or other related genes, or even in the noncoding sequences of the LDL receptor gene.