Decrease in serum nucleotide pyrophosphatase activity in ankylosing spondylitis.
OBJECTIVE
Ankylosing spondylitis (AS) is a prototype of a group of rheumatic diseases referred to as spondyloarthropathy. AS patients show marked ectopic ossification in the spine, occasionally resulting in so-called bamboo spine. Although a strong association with HLA-B27 has been reported, its aetiology remains undetermined. Another rheumatic disease, ossification of the posterior longitudinal ligament of the spine (OPLL), demonstrates ectopic ossification of the spinal ligaments very similar to that of AS. Recently, nucleotide pyrophosphatase (NPPS) was implicated in the aetiology of OPLL: an Npps mutation was found to cause OPLL in mice, and an association between a polymorphism of the human NPPS gene and OPLL was identified. The clinical similarities between AS and OPLL led us to hypothesize that NPPS may also be implicated in the aetiology of AS. To elucidate the role of NPPS in the pathogenesis of AS, we examined serum NPPS activity and the possible association of the NPPS gene with AS.


METHODS
Forty-four Japanese patients with AS, 43 patients with OPLL, and age- and sex-matched normal volunteers took part in this study. We determined serum NPPS activity using high-performance liquid chromatography and examined the association between AS and NPPS using single nucleotide polymorphisms (SNPs) of the NPPS gene.


RESULTS
Serum NPPS activity in AS patients was significantly decreased compared with the controls (P < 0.0001). However, there was no association between AS and NPPS gene SNPs.


CONCLUSIONS
NPPS is implicated in the pathogenesis of AS.
Mori
K
K
Department of Orthopaedic Surgery, Shiga University of Medical Science (SUMS), Tsukinowa-cho, Seta, Otsu, Shiga 520-2192, Japan. kanchi@belle.shiga-med.ac.jp
Chano
T
T
Ikeda
T
T
Ikegawa
S
S
Matsusue
Y
Y
Okabe
H
H
Saeki
Y
Y
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017887:Ossification of Posterior Longitudinal Ligament / Q000201:enzymology; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000097:blood* / Q000235:genetics; D013167:Spondylitis, Ankylosing / Q000201:enzymology*; D018709:Statistics, Nonparametric
D011755:Pyrophosphatases; C021899:nucleotide pyrophosphatase