Inorganic Pyrophosphate Plasma Levels Are Decreased in Pseudoxanthoma Elasticum Patients and Heterozygous Carriers but Do Not Correlate with the Genotype or Phenotype.
Inorganic Pyrophosphate Plasma Levels Are Decreased in Pseudoxanthoma Elasticum Patients and Heterozygous Carriers but Do Not Correlate with the Genotype or Phenotype.
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DOI：
10.3390/jcm12051893
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发表时间：
2023-02-27
影响因子：
3.9
通讯作者：
Vanakker, Olivier M. M.
中科院分区：
文献类型：
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作者：
Van Gils, Matthias;Depauw, Justin;Coucke, Paul J. J.;Aerts, Shari;Verschuere, Shana;Nollet, Lukas;Vanakker, Olivier M. M.
关键词：
弹性假性黄瘤（PXE）是一种罕见的影响软结缔组织的异位钙化疾病，由双等位基因ABCC6突变引起。虽然潜在的病理机制尚不完全清楚，但在PXE患者中已经报道了无机焦磷酸盐（PPi）的循环水平降低，这是一种有效的矿化抑制剂，被认为是一种有用的疾病生物标志物。在这项研究中，我们探讨了PPi、ABCC6基因型和PXE表型之间的关系。为此，我们优化并验证了可在临床环境中使用的带有内部校准的PPi测量方案。对78名PXE患者、69名杂合携带者和14名对照样本的分析显示，尽管所有组之间存在重叠，但三个队列之间测量的PPi水平存在显著差异。与对照组相比，PXE患者PPi水平降低了±50%。同样，我们发现携带者减少了±28%。发现PPi水平与PXE患者和携带者的年龄相关，与ABCC6基因型无关。PPi水平与Phenodex评分之间没有相关性。我们的研究结果表明，除了PPi之外，其他因素也在异位矿化中起作用，这限制了PPi作为严重程度和疾病进展的预测性生物标志物的使用。
Pseudoxanthoma elasticum (PXE) is a rare ectopic calcification disorder affecting soft connective tissues that is caused by biallelic ABCC6 mutations. While the underlying pathomechanisms are incompletely understood, reduced circulatory levels of inorganic pyrophosphate (PPi)—a potent mineralization inhibitor—have been reported in PXE patients and were suggested to be useful as a disease biomarker. In this study, we explored the relation between PPi, the ABCC6 genotype and the PXE phenotype. For this, we optimized and validated a PPi measurement protocol with internal calibration that can be used in a clinical setting. An analysis of 78 PXE patients, 69 heterozygous carriers and 14 control samples revealed significant differences in the measured PPi levels between all three cohorts, although there was overlap between all groups. PXE patients had a ±50% reduction in PPi levels compared to controls. Similarly, we found a ±28% reduction in carriers. PPi levels were found to correlate with age in PXE patients and carriers, independent of the ABCC6 genotype. No correlations were found between PPi levels and the Phenodex scores. Our results suggest that other factors besides PPi are at play in ectopic mineralization, which limits the use of PPi as a predictive biomarker for severity and disease progression.
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DOI：
10.1073/pnas.1319582110
发表时间：
2013-12-10
影响因子：
11.1
作者：
Jansen, Robert S.;Kucukosmanoglu, Asli;van de Wetering, Koen
通讯作者：
van de Wetering, Koen
影响因子：
3.9
作者：
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影响因子：
4.6
作者：
Boraldi, Federica;Annovi, Giulia;Quaglino, Daniela
通讯作者：
Quaglino, Daniela
影响因子：
6.5
作者：
Boraldi, Federica;Annovi, Giulia;Quaglino, Daniela
通讯作者：
Quaglino, Daniela
影响因子：
3.9
作者：
通讯作者：
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