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.
Recently, the FRZB Gly324 variant has been shown to have an attenuated ability to antagonize Wnt signaling and to be associated with an increased osteoarthritis risk.
No direct replication of previous OA association findings was obtained but the results suggest that the R324G SNP of the FRZB gene may have an effect in OA development in multiple joints, with a specific severe involvement of the hip in women.
While power was limited for most studies to date, a meta-analysis of all published studies regarding the FRZBArg324Gly polymorphism was performed for hip- and knee-OA separately.
Our results confirm that the R324G variant of the FRZB gene is involved in OA and indicate a role of this variant in several generalized OA phenotypes.
Our results confirm that the R324G variant of the FRZB gene is involved in OA and indicate a role of this variant in several generalized OA phenotypes.
The FRZB, ASPN and CALM1 results are compelling and highlight that polymorphism in signal transduction pathways is a major component of osteoarthritis susceptibility.
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.
Our data confirm findings of another study, that a rare haplotype with both Arg200Trp and Arg324GlyFRZB variants contributes to the genetic susceptibility to hip OA among Caucasian women, and that these polymorphisms may contribute to increased serum levels of proteins as biomarkers of OA.
Genetic association studies have identified a few consistent osteoarthritis susceptibility genes (FRZB, GDF5, and DIO2) that replicate across different populations.
Our results indicate separate roles for the antagonists, where DKK1 and GREM1 had similarities in response to injury and in OA, with a different response for FRZB.
Replication studies have confirmed association of functional sequence variations in the secreted frizzled-related protein 3 (FRZB) and asporin (ASPN) genes with osteoarthritis.
Single nucleotide polymorphisms (SNPs) in frizzled-related protein (FRZB) have been associated with osteoarthritis, but their association with the risk of skeletal fluorosis has not been reported.
The Expressions of Dickkopf-Related Protein 1 and Frizzled-Related Protein Are Negatively Correlated to Local Inflammation and Osteoarthritis Severity.
Our results indicate that genetic polymorphisms affecting knee OA vary between populations (Japanese versus Caucasian) and sexes and indicate a role for ASPN, COMP, FRZB, and COL2A1 in Caucasians.
The present study demonstrated that WNTs and FRPs are differentially expressed in RA and OA synovium, and suggests an involvement in the pathology of these diseases.