ATP7B基因中的H1069Q突变与威尔逊病的晚期和神经学表现相关：一项荟萃分析的结果

The H1069Q mutation in ATP7B is associated with late and neurologic presentation in Wilson disease: results of a meta-analysis.

作者信息

Stapelbroek Janneke M, Bollen Casper W, van Amstel Johannes K Ploos, van Erpecum Karel J, van Hattum Jan, van den Berg Leonard H, Klomp Leo W J, Houwen Roderick H J

机构信息

Department of Pediatric Gastroenterology, Wilhelmina Children's Hospital, University Medical Center, P.O. Box 85090, 3508 AB Utrecht, The Netherlands.

出版信息

J Hepatol. 2004 Nov;41(5):758-63. doi: 10.1016/j.jhep.2004.07.017.

DOI:10.1016/j.jhep.2004.07.017

PMID:15519648

Abstract

BACKGROUND AND AIMS

Wilson disease is an hereditary disorder of copper metabolism, caused by mutations in the ATP7B gene, and leading to hepatic or neurologic disease. We examined whether H1069Q, the most common ATP7B mutation, is associated with a specific phenotype.

METHODS

Genotyping results in 70 Dutch patients were related to clinical presentation. Subsequently a meta-analysis for genotype-phenotype correlation was performed on all patients available from literature, combined with the current Dutch group, a total of 577 patients.

RESULTS

The Dutch patients homozygous or heterozygous for the H1069Q mutation presented more frequently with neurologic disease (63% and 43% vs. 15%), and at a later age (20.9 and 15.9 vs. 12.6 years) than patients without the H1069Q mutation. In the meta-analysis the odds-ratio for neurologic presentation in homozygous or heterozygous H1069Q vs. non-H1069Q patients was 3.50 (95% CI 2.01-6.09) and 2.13 (95% CI 1.18-3.83), respectively. Age at presentation was 21.1, 19.2 and 16.5 years, respectively, corresponding to a weighted mean difference (WMD) of 4.41 (95% CI 1.56-7.26) for homozygous H1069Q vs. heterozygous patients and 6.68 (95% CI 4.33-9.38) for homozygous H1069Q vs. non-H1069Q patients.

CONCLUSIONS

Our results indicate that the H1069Q mutation is associated with a late and neurologic presentation.

摘要

背景与目的

威尔逊病是一种铜代谢的遗传性疾病，由ATP7B基因突变引起，可导致肝脏或神经系统疾病。我们研究了最常见的ATP7B突变H1069Q是否与特定表型相关。

方法

对70例荷兰患者的基因分型结果与临床表现进行关联分析。随后，对文献中所有可得患者以及当前荷兰患者组（共577例患者）进行基因型-表型相关性的荟萃分析。

结果

H1069Q突变纯合或杂合的荷兰患者出现神经系统疾病的频率更高（分别为63%和43%，而无H1069Q突变患者为15%），且发病年龄更晚（分别为20.9岁和15.9岁，而无H1069Q突变患者为12.6岁）。在荟萃分析中，H1069Q纯合或杂合患者与非H1069Q患者相比，出现神经系统表现的优势比分别为3.50（95%置信区间2.01 - 6.09）和2.13（95%置信区间1.18 - 3.83）。发病年龄分别为21.1岁、19.2岁和16.5岁，H1069Q纯合患者与杂合患者相比，加权平均差（WMD）为4.41（95%置信区间1.56 - 7.26），H1069Q纯合患者与非H1069Q患者相比，加权平均差为6.68（95%置信区间4.33 - 9.38）。