title: Investigation of the role of ENPP1 and TNAP genes in chondrocalcinosis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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 chi(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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Oxford University Institute of Musculoskeletal Sciences, Botnar Research Centre, Nuffield Orthopaedic Centre, Oxford OX3 7LD, UK. yun@well.ox.ac.uk
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: M A
authors.initials: MA
authors.lastname: Brown
authors.forename: C
authors.initials: C
authors.lastname: Peach
authors.forename: G
authors.initials: G
authors.lastname: Russell
authors.forename: B P
authors.initials: BP
authors.lastname: Wordsworth
mesh_terms: D000368:Aged; D000469:Alkaline Phosphatase; D002352:Carrier Proteins / Q000235:genetics*; D002805:Chondrocalcinosis / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; C548267:ALPL protein, human; D000469:Alkaline Phosphatase; D010727:Phosphoric Diester Hydrolases; C065962:ectonucleotide pyrophosphatase phosphodiesterase 1; D011755:Pyrophosphatases