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Allelic expression analysis suggests that cis-acting polymorphism of FRZB expression does not contribute to osteoarthritis susceptibility

Lookup NU author(s): Professor John Loughlin

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Abstract

OBJECTIVE: The FRZB gene codes for secreted frizzled-related protein 3 (sFRP3), a soluble antagonist of wnt signalling that is required for maintaining cartilage integrity. Two common single nucleotide polymorphisms (SNPs) that code for the substitution of conserved arginine residues have previously been identified in FRZB and found to be associated with osteoarthritis (OA). Functional studies revealed that the arginine substitutions lead to a loss-of-function of sFRP3 activity. We set out to assess whether cis-acting polymorphism in the regulation of FRZB expression exists, as this may be an additional mechanism through which sFRP3 activity could be modulated. METHODS: RNA was extracted from the articular cartilage chondrocytes of 25 individuals who had undergone joint replacement for OA and who were heterozygous for one of the two FRZB SNPs. Allelic output was measured by single base extension in to the SNPs and deviations from the expected 1:1 pattern were assessed using the Mann-Whitney U test. RESULTS: Differential allelic expression was observed in six of the 25 individuals. However, the average fold difference in allelic expression in the six was only 1.19. CONCLUSIONS: The presence of a small degree of differential allelic expression in a low proportion (24%) of the individuals studied suggests that polymorphism in FRZB cis-acting regulatory elements can be discounted as a major factor that could influence the development of OA.


Publication metadata

Author(s): Snelling S, Ferreira A, Loughlin J

Publication type: Article

Publication status: Published

Journal: Osteoarthritis and Cartilage

Year: 2007

Volume: 15

Issue: 1

Pages: 90-92

ISSN (print): 1063-4584

ISSN (electronic): 1522-9653

Publisher: Elsevier Ltd

URL: http://dx.doi.org/10.1016/j.joca.2006.06.016

DOI: 10.1016/j.joca.2006.06.016


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