Cuff tear arthropathy: Evidence of functional variation in pyrophosphate metabolism genes

Peach, C.A., Zhang, Y., Dunford, J.E., Brown, M.A., & Carr, A.J. (2007) Cuff tear arthropathy: Evidence of functional variation in pyrophosphate metabolism genes. Clinical Orthopaedics and Related Research, 462(1), pp. 67-72.

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We investigated the role of two genes, ANKH and TNAP, in patients with cuff tear arthropathy. These genes encode proteins which regulate the extracellular concentration of inorganic pyrophosphate, fluctuations of which can lead to calcium crystal formation. Variants were detected by direct sequencing of DNA and their frequencies compared with healthy controls. The effect of variants on protein function was further studied by in vitro approaches. Variant genotypes were observed more frequently in the cases when compared with controls in ANKH (45% and 20%) and TNAP (32% and 9%). Variants in ANKH altered inorganic pyrophosphate (PPi) concentrations in transfected human chondrocytes. There was a higher mean serum concentration of TNAP detected in female patients compared with normal ranges. Cuff tear arthropathy is associated with variants in ANKH and TNAP that alter extracellular inorganic pyrophosphate concentrations causing calcium crystal deposition. This supports a theory that genetic variants predispose patients to primary crystal deposition which when combined with a massive rotator cuff tear leads to the development of arthritis.

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9 citations in Web of Science®

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ID Code: 87997
Item Type: Journal Article
Refereed: Yes
Keywords: protein, protein ANKH, protein TNAP, pyrophosphate, unclassified drug, ANKH protein, human, carrier protein, phosphate transporter, TNAP protein, human, arthropathy, article, clinical article, controlled study, DNA sequence, female, genetic variability, human, male, priority journal, protein function, rotator cuff rupture, blood, cartilage cell, cell culture, chondrocalcinosis, genetic predisposition, genetic transfection, genetics, injury, metabolism, pathology, rotator cuff, sex difference, shoulder, single nucleotide polymorphism, Carrier Proteins, Cells, Cultured, Chondrocytes, Diphosphates, Genetic Predisposition to Disease, Humans, Phosphate Transport Proteins, Polymorphism, Single Nucleotide, Sequence Analysis, DNA, Sex Factors, Shoulder Joint, Transfection
ISSN: 0009-921X
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 02 Oct 2015 02:10
Last Modified: 16 Oct 2015 08:29

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