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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.

Original publication

DOI

10.1097/blo.0b013e31811f39de

Type

Journal article

Journal

Clinical orthopaedics and related research

Publication Date

09/2007

Volume

462

Pages

67 - 72

Addresses

Nuffield Department of Orthopaedic Surgery, University of Oxford, Headington, Oxford, England. c.peach@doctors.org.uk

Keywords

Shoulder Joint, Cells, Cultured, Chondrocytes, Humans, Chondrocalcinosis, Genetic Predisposition to Disease, Diphosphates, Carrier Proteins, Phosphate Transport Proteins, Transfection, Sequence Analysis, DNA, Sex Factors, Polymorphism, Single Nucleotide, Female, Male, Rotator Cuff Injuries