The S18Y polymorphism in the UCHL1 gene is a genetic modifier in Huntington's disease
The S18Y polymorphism in the UCHL1 gene is a genetic modifier in Huntington's disease
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DOI：
10.1007/s10048-005-0023-z
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发表时间：
2006-03-01
期刊：
影响因子：
2.2
通讯作者：
Riess, O
中科院分区：
文献类型：
--
作者：
Metzger, S;Bauer, P;Riess, O
亨廷顿蛋白中一段扩展的聚谷氨酰胺延伸已被确定为亨廷顿病(HD)的致病原因。尽管扩展的聚谷氨酰胺重复序列的长度与发病年龄呈负相关，但其他遗传因素被认为改变了疾病发病的差异。由于连锁分析提示在染色体4p上有一个修饰基因，我们调查了946例高加索人HD患者泛素羧基末端水解酶L1基因S18Y多态的功能相关性。在本组中，S18Y基因座上的等位基因变异可解释1.1%的HD发病年龄变异，罕见的Y等位基因与较年轻的病例相关。
An expanded polyglutamine stretch in the huntingtin protein has been identified as the pathogenetic cause of Huntington's disease (HD). Although the length of the expanded polyglutamine repeat is inversely correlated with the age-at-onset, additional genetic factors are thought to modify the variance in the disease onset. As linkage analysis suggested a modifier locus on chromosome 4p, we investigated the functional relevance of S18Y polymorphism of the ubiquitin carboxy-terminal hydrolase L1 in 946 Caucasian HD patients. In this group, the allelic variation on locus S18Y is responsible for 1.1% of the variance in the HD age-at-onset, and the rare Y allele is associated with younger-aged cases.