Retinol (vitamin A) and retinol-binding protein levels are decreased in ankylosing spondylitis: clinical and genetic analysis.
OBJECTIVE
Retinol (vitamin A) plays an important role in bone structure and function. Treatment with retinoids has been associated with bone abnormalities mimicking spondyloarthropathy and diffuse idiopathic skeletal hyperostosis. To determine whether retinol concentrations are altered in patients with ankylosing spondylitis (AS), we examined serum retinol levels in patients with AS and healthy controls.


METHODS
Retinol was assessed using mass spectrometry, and retinol-binding protein levels were assessed by ELISA. Retinol levels were correlated with clinical disease activity indices. The CYP26 gene, which plays a key role in retinol metabolism, was examined to define any single-nucleotide polymorphisms (SNP) associations with AS.


RESULTS
Retinol levels were significantly lower in the AS cohort than in controls (mean 2.39 +/- 0.88 micromol/l for AS, 3.34 +/- 1.01 micromol/l for controls; p < 0.0001). Retinol-binding protein levels were also lower in AS than controls (AS 4.65 +/- 2.10 microg/l; controls 7.48 +/- 4.87 microg/l; p < 0.001). Serum retinol levels did not correlate with indices of disease activity defined serologically (C-reactive protein, erythrocyte sedimentation rate) or clinically (Bath AS Disease Activity Index, Bath AS Functional Index). Genetic analysis showed that an exonic CYP26C1 SNP (rs11187265) is not associated with AS.


CONCLUSIONS
The hallmark of AS is neo-ossification. AS is associated with abnormal serum levels of retinol, a biochemical factor linked to pathological hyperostosis. Further genetic studies are warranted into the genetic basis of the retinol-AS relationship.
University Health Network, University of Toronto, Toronto, Ontario, Canada.
Finbar D
FD
O'Shea
Florence W L
FW
Tsui
Basil
B
Chiu
Hing Wo
HW
Tsui
Mehrdad
M
Yazdanpanah
Robert D
RD
Inman
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000072516:Retinoic Acid 4-Hydroxylase; D054839:Retinol-Binding Proteins, Plasma / Q000032:analysis* / Q000235:genetics; D013167:Spondylitis, Ankylosing / Q000097:blood* / Q000235:genetics*; D014801:Vitamin A / Q000097:blood* / Q000235:genetics
D054839:Retinol-Binding Proteins, Plasma; D014801:Vitamin A; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase