Preferential X chromosome loss but random inactivation characterize primary biliary cirrhosis
Preferential X chromosome loss but random inactivation characterize primary biliary cirrhosis
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DOI：
10.1002/hep.21696
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发表时间：
2007-08-01
期刊：
影响因子：
13.5
通讯作者：
Invernizzi, Pietro
中科院分区：
文献类型：
--
作者：
Miozzo, Monica;Selmi, Carlo;Invernizzi, Pietro
最近的研究表明，原发性胆汁性肝硬化（PBC）以及其他两种女性占主导地位的自身免疫性疾病，系统性硬化症和自身免疫性甲状腺疾病的女性X单体性增强。为了进一步了解这些事件，我们研究了166名PBC女性和226名严格年龄匹配的健康和肝病对照者的X染色体丢失和X染色体失活（XCI）机制。用4个X连锁短串联重复序列的荧光定量聚合酶链反应（QF-PCR）进行X染色体分析和缺失模式的确定。XCI的进一步定义是基于对甲基化敏感的限制性位点的分析。重要的是，在PBC中，X染色体丢失不仅发生得更频繁，而且以优先的方式发生。这一观察结果支持了我们的论点，即增强的X单体性仅涉及一个亲本衍生的染色体，并且不继发于XCI的组成性非随机模式。事实上，在单体性存在的情况下，丢失的X染色体必然是无活性的同源体。结论：X染色体丢失是优先的这一发现表明，X染色体基因产物在女性PBC易感性中的重要参与，也强调了需要确定维持染色体的父母来源以研究印记的作用。
Recent work has demonstrated enhanced X monosomy in women with primary biliary cirrhosis (PBC as well as two other female-predominant autoimmune diseases, systemic sclerosis and autoimmune thyroid disease. To further our understanding of these events, we have investigated the mechanisms of X chromosome loss and X chromosome inactivation (XCI) in 166 women with PBC and 226 rigorously age-matched healthy and liver disease controls. X chromosome analysis and determination of loss pattern was performed by quantitative fluorescent polymerase chain reaction (QF-PCR) with 4 X-linked short tandem repeats. Further definition of the XCI was based on analysis of methylation-sensitive restriction sites. Importantly, in PBC the X chromosome loss occurs not only more frequently but also in a preferential fashion. This observation supports our thesis that the enhanced X monosomy involves only one parentally derived chromosome and is not secondary to a constitutive non random pattern of XCI. In fact, in the presence of monosomy, the lost X chromosome is necessarily the inactive homologue. Conclusion: The finding that the X chromosome loss is preferential suggests the critical involvement of X chromosome gene products in the female predisposition to PBC and also emphasizes the need to determine the parental origin of the maintained chromosome to investigate the role of imprinting.