Analytical Validation of Familial Hypercholesterolemia Biomarkers in Dried Blood Spots.
Analytical Validation of Familial Hypercholesterolemia Biomarkers in Dried Blood Spots.
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DOI：
10.3390/ijns8010014
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发表时间：
2022-02-09
影响因子：
3.5
通讯作者：
Peterson A
中科院分区：
文献类型：
--
作者：
Held PK;Campbell K;Wiberley-Bradford AE;Lasarev M;Horner V;Peterson A
杂合子家族性高胆固醇血症（HeFH）是一种常见的，可治疗的遗传性疾病，其特征是过早的动脉粥样硬化和心血管疾病，但大多数受影响的个体仍未确诊。新生儿筛查可以在识别高危个体方面发挥作用，并在症状出现之前提供早期干预的机会。本研究的目的是开发和验证用于定量干血斑（DBS）中候选HeFH生物标志物的测定法。市售酶测定试剂盒定量血清总胆固醇（TC）和低密度脂蛋白胆固醇（LDL-C）进行了修改DBS的高通量分析。DBS中的载脂蛋白B（Apo B）浓度采用免疫测定法测量，该方法对已发表的研究进行了修改。根据美国病理学家学会临床实验室指南，对所有三种测定法进行了验证。通过精密度、回收率、定量限（LOQ）和线性评估TC、LDL-C和ApoB测定的性能。精密度研究得出的变异系数（CV）小于15%，所有三种测定的回收率均大于75%。测定的LOQ和线性与基于血清的测定相当。在血清和DBS浓度之间的直接比较中，证明了TC、LDL-C和ApoB的正相关性。此外，未受影响人群中三种生物标志物浓度的初始评价与先前发表的研究中获得的值相似。本研究报告了DBS中TC、LDL-C和ApoB的定量方法。测定验证结果在新生儿筛查的可接受限度内。这是识别新生儿HeFH的重要第一步。
Heterozygous familial hypercholesterolemia (HeFH) is a common, treatable genetic disorder characterized by premature atherosclerosis and cardiovascular disease, yet the majority of affected individuals remain undiagnosed. Newborn screening could play a role in identification of at-risk individuals and provide an opportunity for early intervention, prior to the onset of symptoms. The objective of this study was to develop and validate assays for quantification of candidate HeFH biomarkers in dried blood spots (DBS). Commercially available enzyme assay kits for quantification of serum total cholesterol (TC) and low-density lipoprotein-cholesterol (LDL-C) were modified for high-throughput analysis of DBS. Apolipoprotein B (ApoB) concentrations in DBS were measured using an immunoassay with modifications from published studies. All three assays were validated according to the College of American Pathologists guidelines for clinical laboratories. The performance of TC, LDL-C, and ApoB assays was assessed by precision, recovery, limit of quantification (LOQ) and linearity. Precision studies yielded coefficients of variation (CV) of less than 15%, with recovery greater than 75% for all three assays. The determined LOQ and linearity were comparable to serum-based assays. In a direct comparison between serum and DBS concentrations, positive correlations were demonstrated for TC, LDL-C, and ApoB. Additionally, the initial evaluation of the three biomarker concentrations within the unaffected population was similar to values obtained in previous published studies. This study reports on methods for quantification of TC, LDL-C, and ApoB in DBS. Assay validation results were within acceptable limits for newborn screening. This is an important first step toward the identification of newborns with HeFH.
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影响因子：
39.3
作者：
Nordestgaard BG;Chapman MJ;Humphries SE;Ginsberg HN;Masana L;Descamps OS;Wiklund O;Hegele RA;Raal FJ;Defesche JC;Wiegman A;Santos RD;Watts GF;Parhofer KG;Hovingh GK;Kovanen PT;Boileau C;Averna M;Borén J;Bruckert E;Catapano AL;Kuivenhoven JA;Pajukanta P;Ray K;Stalenhoef AF;Stroes E;Taskinen MR;Tybjærg-Hansen A;European Atherosclerosis Society Consensus Panel
通讯作者：
European Atherosclerosis Society Consensus Panel
影响因子：
1.3
作者：
Eick, Geeta N.;Kowal, Paul;Snodgrass, J. Josh
通讯作者：
Snodgrass, J. Josh
影响因子：
9.8
作者：
GLUECK, CJ;HECKMAN, F;PEARCE, W
通讯作者：
PEARCE, W
对家族性高胆固醇血症的儿童父母筛查和级联测试的整合。
影响因子：
2.9
作者：
Wald DS;Wald NJ
通讯作者：
Wald NJ
影响因子：
4.4
作者：
Goldberg, Anne C.;Hopkins, Paul N.;Ziajka, Paul E.
通讯作者：
Ziajka, Paul E.