通过预测发病年龄来标准化亨廷顿病的CAP评分。

IF 2.1 Q3 NEUROSCIENCES Journal of Huntington's disease Pub Date : 2022-04-19 DOI:10.3233/jhd-210475
John H. Warner, J. Long, J. Mills, D. Langbehn, Jennifer J. Ware, A. Mohan, C. Sampaio
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引用次数: 8

摘要

背景:亨廷顿氏病(HD)是一种常染色体显性的神经系统疾病,由亨廷顿蛋白(HTT)基因n端附近CAG重复扩增引起。关于HD病因学的一个主要理论是,发病和进展都是由突变(或CAG扩展)亨廷顿蛋白(mHTT)的累积暴露所驱动的。CAG- age - product (CAP)评分(即,过量CAG长度和年龄的乘积)是这种累积暴露的常用测量方法。CAP评分已被广泛用作HD中各种疾病状态变量的预测因子。然而,由于对CAP分数的精确定义缺乏共识,它的效用已经有所减弱。最常用的CAP分数形式是高度相关的,因此,为了预测的目的,使用哪种形式几乎没有区别。然而,根据常用的定义,报告的CAP分数值在应用于相同的数据时,在量级上存在很大差异。这使研究间比较的过程变得复杂。目的提出一种标准化的CAP评分定义,以解决这一难题。我们的标准化是这样选择的,在预期的诊断年龄CAP = 100。方法统计方法包括将新的生存分析方法应用于从Enroll-HD数据库(PDS 5)中获取的13个疾病标志,并与现有的金标准发病模型进行比较。结果:我们工作的有益副产品包括最新的发病年龄(AO)结果和适用于其他情况的精炼AO模型,讨论了以前文献中未提到的CAP评分的几个有用特性,并引入了毒性发病模型的概念。结论采用L = 30和K = 6.49的CAP评分标准,可用于HD临床数据的常规建模。
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Standardizing the CAP Score in Huntington's Disease by Predicting Age-at-Onset.
BACKGROUND Huntington's disease (HD) is an autosomal dominant, neurological disease caused by an expanded CAG repeat near the N-terminus of the huntingtin (HTT) gene. A leading theory concerning the etiology of HD is that both onset and progression are driven by cumulative exposure to the effects of mutant (or CAG expanded) huntingtin (mHTT). The CAG-Age-Product (CAP) score (i.e., the product of excess CAG length and age) is a commonly used measure of this cumulative exposure. CAP score has been widely used as a predictor of a variety of disease state variables in HD. The utility of the CAP score has been somewhat diminished, however, by a lack of agreement on its precise definition. The most commonly used forms of the CAP score are highly correlated so that, for purposes of prediction, it makes little difference which is used. However, reported values of CAP scores, based on commonly used definitions, differ substantially in magnitude when applied to the same data. This complicates the process of inter-study comparison. OBJECTIVE In this paper, we propose a standardized definition for the CAP score which will resolve this difficulty. Our standardization is chosen so that CAP = 100 at the expected age of diagnosis. METHODS Statistical methods include novel survival analysis methodology applied to the 13 disease landmarks taken from the Enroll-HD database (PDS 5) and comparisons with the existing, gold standard, onset model. RESULTS Useful by-products of our work include up-to-date, age-at-onset (AO) results and a refined AO model suitable for use in other contexts, a discussion of several useful properties of the CAP score that have not previously been noted in the literature and the introduction of the concept of a toxicity onset model. CONCLUSION We suggest that taking L = 30 and K = 6.49 provides a useful standardization of the CAP score, suitable for use in the routine modeling of clinical data in HD.
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来源期刊
CiteScore
4.80
自引率
9.70%
发文量
60
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