Investigation of the role of ENPP1 and TNAP genes in chondrocalcinosis

Zhang, Y., Brown, M. A., Peach, C., Russell, G., & Wordsworth, B. P. (2007) Investigation of the role of ENPP1 and TNAP genes in chondrocalcinosis. Rheumatology, 46(4), pp. 586-589.

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Extracellular inorganic pyrophosphate (ePPi) inhibits certain forms of pathological mineralization while promoting others. Three molecules involved in ePPi regulation are important candidates for the development of calcium pyrophosphate dihydrate chondrocalcinosis (CPPD CC). These include ANKH, ectonucleotide pyrophosphatase (ENPP1) and TNAP. We have previously showed that genetic variation in ANKH is a cause of autosomal dominant familial CC and also some sporadic cases of CPPD CC. We now investigate the possible role of ENPP1 and TNAP in CPPD CC.


Exons, untranslated regions (UTR) and exon-intron boundaries of ENPP1 and TNAP were sequenced using ABI Big Dye chemistry on automated sequencers. Sixteen variants were identified (3 in ENPP1 and 13 in TNAP) and were subsequently genotyped in 128 sporadic Caucasian CPPD CC patients and 600 healthy controls using a combination of polymerase chain reaction/restriction fragment-length polymorphism analysis or using Taqman. Allele and genotype frequencies were compared between cases and controls using the χ 2 test. Linkage disequilibrium, haplotype and the single nucleotide polymorphism-specific analyses were also performed. This study had 80% power to detect an odds ratio of 2.2 or more at these loci. Results. No difference was observed in the allele or genotype frequencies between patients and controls at either ENPP1 or TNAP.


Polymorphisms of ENPP1 and TNAP are not major determinants of susceptibility to CC in the population studied. Further studies of the aetiology of sporadic CPPD CC are required to determine its causes.

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ID Code: 89468
Item Type: Journal Article
Refereed: Yes
Additional Information: Cited By :12
Export Date: 21 September 2015
Correspondence Address: Zhang, Y.; Oxford University Institute of Musculoskeletal Sciences, Botnar Research Centre, Nuffield Orthopaedic Centre, Oxford OX3 7LD, United Kingdom; email:
Keywords: ANKH, ENPP1, Pseudogout, Pyrophosphate arthropathy, TNAP, calcium pyrophosphate, ectonucleotide pyrophosphatase 1, phosphatase, tissue nonspecific alkaline phosphatase, unclassified drug, adult, article, Caucasian, chi square test, controlled study, exon, gene frequency, gene function, gene linkage disequilibrium, gene locus, gene sequence, genetic susceptibility, genetic variability, genotype, haplotype, human, human cell, intron, major clinical study, polymerase chain reaction, priority journal, restriction fragment length polymorphism, single nucleotide polymorphism, untranslated region, Aged, Carrier Proteins, Chondrocalcinosis, Genetic Predisposition to Disease, Humans, Middle Aged, Mutation, Phosphoric Diester Hydrolases, Polymorphism, Single Nucleotide, Pyrophosphatases
DOI: 10.1093/rheumatology/kel338
ISSN: 1462-0324
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: © 2007 Oxford University Press
Deposited On: 25 Oct 2015 23:43
Last Modified: 19 Aug 2016 01:00

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