Gu Yan-Hong, Kodama Hiroko, Du Si-Lian
Department of Pediatrics, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173-8605, Japan.
Brain Dev. 2005 Dec;27(8):551-3. doi: 10.1016/j.braindev.2005.01.006.
Wilson's disease (WD) is an autosomal recessive disorder of copper metabolism caused by a large number of different mutations in the ATP7B gene. R778L mutation is mostly observed in Chinese, Japanese and Korean patients, whereas the H1069Q point mutation in the ATP7B gene is the most frequent mutation in European patients with WD. In our previous study we did not find a significant correlation between genotype and phenotype (age of onset and clinical presentation) in patients homozygous (37 patients) or heterozygous (52 patients) for R778L. It was reported that European patients homozygous for H1069Q who were also homozygous for the ApoE genotype epsilon3/3 developed clinical symptoms 5-11 years later than did patients with genotypes other than ApoE epsilon3/3. In the present study (i) we firstly observed that ApoE epsilon3/3 did not delay the onset of WD; (ii) no association between ApoE genotype and WD clinical presentation in Chinese Han children, including those patients homozygous for R778L. Thus we conclude that the onset of WD in Chinese children is not related to ApoE epsilon3/3, although the high frequency of ApoE epsilon3/3 in Chinese Han children with WD was not significantly different from that in controls.
威尔逊病(WD)是一种常染色体隐性铜代谢紊乱疾病,由ATP7B基因的大量不同突变引起。R778L突变在中国、日本和韩国患者中最为常见,而ATP7B基因中的H1069Q点突变是欧洲WD患者中最常见的突变。在我们之前的研究中,我们没有发现R778L纯合子(37例患者)或杂合子(52例患者)的基因型与表型(发病年龄和临床表现)之间存在显著相关性。据报道,H1069Q纯合且ApoE基因型为epsilon3/3的欧洲患者出现临床症状的时间比ApoE基因型不是epsilon3/3的患者晚5至11年。在本研究中,(i)我们首先观察到ApoE epsilon3/3不会延迟WD的发病;(ii)在中国汉族儿童中,包括R778L纯合子患者,ApoE基因型与WD临床表现之间没有关联。因此我们得出结论,中国儿童WD的发病与ApoE epsilon3/3无关,尽管WD中国汉族儿童中ApoE epsilon3/3的高频率与对照组没有显著差异。