Merle Uta, Stremmel Wolfgang, Gessner Reinhard
Department of Gastroenterology and Hepatology, University Hospital, Heidelberg, Germany.
Arch Neurol. 2006 Jul;63(7):982-5. doi: 10.1001/archneur.63.7.982.
The clinical heterogeneity of Wilson disease expression cannot be fully explained by the various mutations of the Wilson disease gene. The prion-related protein (PrP) has been shown to bind copper in vitro and might therefore influence Wilson disease.
To examine the effect of the PrP polymorphism at codon 129, resulting in either methionine or valine (M129V), on the clinical phenotype of patients with Wilson disease.
Retrospective cross-sectional study at a university hospital.
A total of 134 patients were grouped according to their PrP M129V genotypes and initial clinical symptoms (hepatic vs neurological).
The onset of symptoms was significantly delayed in patients homozygous for the 129M allele as compared with patients with at least 1 V allele (mean +/- SD age, 20.90 +/- 11.9 years vs 15.5 +/- 7.6 years; P = .003). No significant correlation was found when analyzing the impact of the PrP M129V genotype on the clinical symptoms at initial manifestation (hepatic vs neurological; P = .44).
This study shows for the first time, to our knowledge, that the human PrP polymorphism M129V influences the onset of symptoms in patients with the copper storage disorder Wilson disease.
威尔逊病临床表现的异质性不能完全由威尔逊病基因的各种突变来解释。朊病毒相关蛋白（PrP）已被证明在体外能结合铜，因此可能影响威尔逊病。
研究129密码子处导致甲硫氨酸或缬氨酸（M129V）的PrP多态性对威尔逊病患者临床表型的影响。
在一家大学医院进行的回顾性横断面研究。
134例患者根据其PrP M129V基因型和初始临床症状（肝脏型与神经型）分组。
与至少有1个V等位基因的患者相比，129M等位基因纯合患者的症状发作明显延迟（平均±标准差年龄，20.90±11.9岁对15.5±7.6岁；P = 0.003）。分析PrP M129V基因型对初始表现时临床症状（肝脏型与神经型；P = 0.44）的影响时，未发现显著相关性。
据我们所知，本研究首次表明人类PrP多态性M129V会影响铜贮积症威尔逊病患者的症状发作。
