Inorganic Pyrophosphate Plasma Levels Are Decreased in Pseudoxanthoma Elasticum Patients and Heterozygous Carriers but Do Not Correlate with the Genotype or Phenotype
Pseudoxanthoma elasticum (PXE) is a rare ectopic calcification disorder affecting soft connective tissues that is caused by biallelic <i>ABCC6</i> mutations. While the underlying pathomechanisms are incompletely understood, reduced circulatory levels of inorganic pyrophosphate (PPi)—a po...
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| Format: | Article |
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MDPI AG
2023-02-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/12/5/1893 |
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| author | Matthias Van Gils Justin Depauw Paul J. Coucke Shari Aerts Shana Verschuere Lukas Nollet Olivier M. Vanakker |
| author_facet | Matthias Van Gils Justin Depauw Paul J. Coucke Shari Aerts Shana Verschuere Lukas Nollet Olivier M. Vanakker |
| author_sort | Matthias Van Gils |
| collection | DOAJ |
| description | Pseudoxanthoma elasticum (PXE) is a rare ectopic calcification disorder affecting soft connective tissues that is caused by biallelic <i>ABCC6</i> 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 <i>ABCC6</i> 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 <i>ABCC6</i> 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. |
| first_indexed | 2024-03-11T07:20:53Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-11T07:20:53Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-bd85f1f2feb54d319f35fb9f06995c602023-11-17T07:59:46ZengMDPI AGJournal of Clinical Medicine2077-03832023-02-01125189310.3390/jcm12051893Inorganic Pyrophosphate Plasma Levels Are Decreased in Pseudoxanthoma Elasticum Patients and Heterozygous Carriers but Do Not Correlate with the Genotype or PhenotypeMatthias Van Gils0Justin Depauw1Paul J. Coucke2Shari Aerts3Shana Verschuere4Lukas Nollet5Olivier M. Vanakker6Center for Medical Genetics, Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, BelgiumGhent Ectopic Mineralization Research Group, 9000 Ghent, BelgiumCenter for Medical Genetics, Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, BelgiumCenter for Medical Genetics, Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, BelgiumCenter for Medical Genetics, Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, BelgiumCenter for Medical Genetics, Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, BelgiumCenter for Medical Genetics, Ghent University Hospital, Corneel Heymanslaan 10, 9000 Ghent, BelgiumPseudoxanthoma elasticum (PXE) is a rare ectopic calcification disorder affecting soft connective tissues that is caused by biallelic <i>ABCC6</i> 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 <i>ABCC6</i> 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 <i>ABCC6</i> 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.https://www.mdpi.com/2077-0383/12/5/1893<i>ABCC6</i>heterozygous carriersinorganic pyrophosphatepseudoxanthoma elasticumgenotype–phenotype correlationbiomarker |
| spellingShingle | Matthias Van Gils Justin Depauw Paul J. Coucke Shari Aerts Shana Verschuere Lukas Nollet Olivier M. Vanakker Inorganic Pyrophosphate Plasma Levels Are Decreased in Pseudoxanthoma Elasticum Patients and Heterozygous Carriers but Do Not Correlate with the Genotype or Phenotype Journal of Clinical Medicine <i>ABCC6</i> heterozygous carriers inorganic pyrophosphate pseudoxanthoma elasticum genotype–phenotype correlation biomarker |
| title | Inorganic Pyrophosphate Plasma Levels Are Decreased in Pseudoxanthoma Elasticum Patients and Heterozygous Carriers but Do Not Correlate with the Genotype or Phenotype |
| title_full | Inorganic Pyrophosphate Plasma Levels Are Decreased in Pseudoxanthoma Elasticum Patients and Heterozygous Carriers but Do Not Correlate with the Genotype or Phenotype |
| title_fullStr | Inorganic Pyrophosphate Plasma Levels Are Decreased in Pseudoxanthoma Elasticum Patients and Heterozygous Carriers but Do Not Correlate with the Genotype or Phenotype |
| title_full_unstemmed | Inorganic Pyrophosphate Plasma Levels Are Decreased in Pseudoxanthoma Elasticum Patients and Heterozygous Carriers but Do Not Correlate with the Genotype or Phenotype |
| title_short | Inorganic Pyrophosphate Plasma Levels Are Decreased in Pseudoxanthoma Elasticum Patients and Heterozygous Carriers but Do Not Correlate with the Genotype or Phenotype |
| title_sort | inorganic pyrophosphate plasma levels are decreased in pseudoxanthoma elasticum patients and heterozygous carriers but do not correlate with the genotype or phenotype |
| topic | <i>ABCC6</i> heterozygous carriers inorganic pyrophosphate pseudoxanthoma elasticum genotype–phenotype correlation biomarker |
| url | https://www.mdpi.com/2077-0383/12/5/1893 |
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