Phosphorylated neurofilament heavy chain is a marker of neurodegeneration in Leber hereditary optic neuropathy (LHON)
Phosphorylated neurofilament heavy chain is a marker of neurodegeneration in Leber hereditary optic neuropathy (LHON)
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发表时间：
2008-12
期刊：
影响因子：
2.2
通讯作者：
J. Guy;G. Shaw;F. Ross-Cisneros;P. Quiros;S. Salomão;A. Berezovsky;V. Carelli;W. Feuer;A. Sadun
中科院分区：
文献类型：
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作者：
J. Guy;G. Shaw;F. Ross-Cisneros;P. Quiros;S. Salomão;A. Berezovsky;V. Carelli;W. Feuer;A. Sadun
目的探讨Leber遗传性视神经病变（LHON）的神经变性特征。方法我们定量了一个巴西家系的16名LHON患者和59名LHON携带者的磷酸化神经丝重链（pNF-H）血清水平，这两名患者的分子特征都是线粒体基因组核苷酸11，778处存在G至A突变。采用多元回归研究受试者特征与pNF-H水平的相关性;对pNF-H数据进行平方根转换，以实现残差分布的正态性。采用Pearson相关分析和双样本t检验对各组内pNF-H的平方根与年龄和性别的关系进行了研究。线性回归用于评估组间差异，并确定受影响个体和携带者之间的年龄关系是否不同。根据年龄绘制pNF-H水平的结果表明非线性二次相关，因此在统计分析中使用年龄平方。采用协方差分析评估年龄和组别对pNF-H水平的影响。结果在携带者组中，pNF-H的平方根（均值为0.24ng/ml ~ 2）与年龄呈显著相关（r=0.30，p=0.022），与平方年龄的相关性更强（r=0.37，p=0.003）。受累组的平均pNF-H较高（0.33 ng/ml 2），相关性相似，但无统计学显著性：年龄（r=0.22，p=0.42），二次年龄（r=0.22，p=0.45）。在非家系组中，年龄与pNF-H水平（平均值=0.34 ng/ml 2）之间无相关性：年龄（r=0.03，p=0.87），二次年龄（r=0.04，p=0.84）。在任何组中，性别和pNF-H水平之间均无差异（受累，p=0.65;携带者，p=0.19;非家系，p=0.93）。结论部分LHON患者血清中pNF-H水平升高可能提示视功能丧失后发生了轴索变性。携带者pNF-H水平随年龄增加而增加，在非家系对照中未见，可能提示轻微的亚临床视神经变性。
Purpose To determine the profile of neurodegeneration in Leber hereditary optic neuropathy (LHON). Methods We quantitated serum levels of phosphorylated neurofilament heavy chain (pNF-H) in a Brazilian pedigree of 16 affected patients and 59 carriers with LHON, both molecularly characterized as harboring the G to A mutation at nucleotide 11,778 of the mitochondrial genome. The association of subject characteristics to pNF-H levels was studied with multiple regression; pNF-H data were square-root transformed to effect normality of distribution of residuals. Relationships between the square-root of pNF-H and age and sex were investigated within groups with Pearson correlation and the two-sample t-test. Linear regression was used to assess the difference between groups and to determine if the relationship of age was different between affected individuals and carriers. Results of plotting pNF-H levels by age suggested a nonlinear, quadratic association so age squared was used in the statistical analysis. ANCOVA was used to assess the influence of age and group on pNF-H levels. Results In the carrier group, there was a significant correlation of square-root pNF-H (mean=0.24 ng/ml2) with age (r=0.30, p=0.022) and a stronger correlation with quadratic age (r=0.37, p=0.003). With a higher mean pNF-H (0.33 ng/ml2) for the affected group, correlations were of similar magnitude, although they were not statistically significant: age (r=0.22, p=0.42), quadratic age (r=0.22, p=0.45). There was no correlation between age and pNF-H levels (mean=0.34 ng/ml2) in the off-pedigree group: age (r=0.03, p=0.87), quadratic age (r=0.04, p=0.84). There was no difference between sexes and pNF-H levels in any of the groups (affected, p=0.65; carriers, p=0.19; off-pedigree, p=0.93). Conclusions Elevated pNF-H released into the serum of some affected LHON patients may suggest that axonal degeneration occurs at some point after loss of visual function. Increases in pNF-H levels of carriers with increasing age, not seen in off-pedigree controls, may suggest subtle subclinical optic nerve degeneration.