Liver function in Huntington's disease assessed by blood biochemical analyses in a clinical setting
Liver function in Huntington's disease assessed by blood biochemical analyses in a clinical setting
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DOI：
10.1016/j.jns.2016.02.018
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发表时间：
2016-03-15
影响因子：
4.4
通讯作者：
Josefsen, Knud
中科院分区：
文献类型：
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作者：
Nielsen, Signe Marie Borch;Vinther-Jensen, Tua;Josefsen, Knud
亨廷顿病（HD）是一种显性遗传的进行性神经系统疾病，由亨廷顿基因中的CAG重复序列延长引起。除了运动、精神和认知功能障碍外，还可观察到代谢变化和细胞功能障碍形式的外周疾病表现。在HD患者中分析了各种激素、代谢物和蛋白质的血液水平，确定了与疾病相关的几种变化。然而，尚未进行全面的肝功能检查（LFT）。我们使用临床应用的一组LFT研究了一组显性和预显性HD基因扩增携带者和对照。在这里，我们证明了显式HD基因扩增载体的碱性磷酸酶水平增加相比，premanifest HD基因扩增载体，并与统一的亨廷顿的疾病评定量表-总功能能力评分（UHDRS-TFC）所示的疾病严重程度增加。对于γ-谷氨酰转移酶，明显组中水平升高的频率高于HD基因扩增阴性对照组和明显前HD基因扩增携带者。最后，显性HD基因扩增携带者相对于预先显性HD基因扩增携带者显示出总胆固醇和血糖的中度增加，以及相对于HD基因扩增阴性对照增加的C反应蛋白。我们的研究结果表明，LFT值升高更频繁的表现相比，premanifest HD基因扩增载体和控制。大多数显性HD基因扩增携带者接受药物治疗，这可能会影响本研究中进行的肝功能检查。(C)© 2016 Elsevier B. V.版权所有。
Huntington's disease (HD) is a dominantly inherited, progressive neurological disorder caused by a CAG repeat elongation in the huntingtin gene. In addition to motor-, psychiatric- and cognitive dysfunction, peripheral disease manifestations in the form of metabolic changes and cellular dysfunction are seen. Blood levels of a wide range of hormones, metabolites and proteins have been analyzed in HD patients, identifying several changes associated with the disease. However, a comprehensive panel of liver function tests (LFT) has not been performed. We investigated a cohort of manifest and premanifest HD gene-expansion carriers and controls, using a clinically applied panel of LFTs. Here, we demonstrate that the level of alkaline phosphatase is increased in manifest HD gene-expansion carriers compared to premanifest HD gene-expansion carriers and correlate with increased disease severity indicated by the Unified Huntington's disease rating scale-Total Functional Capacity Score (UHDRS-TFC). For gamma-glutamyl transferase, elevated levels were more frequent in the manifest groups than in both the HD gene-expansion negative controls and premanifest HD gene-expansion carriers. Finally, the manifest HD gene-expansion carriers displayed moderate increases in total cholesterol and blood glucose relative to the premanifest HD gene-expansion carriers, as well as increased C-reactive protein relative to HD gene-expansion negative controls. Our results show that LFT values are elevated more frequently in manifest compared to premanifest HD gene-expansion carriers and controls. The majority of the manifest HD gene-expansion carriers receive medication, and it is possible that this can influence the liver function tests performed in this study. (C) 2016 Elsevier B.V. All rights reserved.