Evidence for a differential association of the Arg200Trp single-nucleotide polymorphism in FRZB with hip osteoarthritis and osteoporosis

Lories, Rik; Boonen, Steven; Peeters, J; Vlam, Kurt de; Luyten, Frank P.

doi:10.1093/rheumatology/kei148

Cited by 39 publications

(30 citation statements)

References 11 publications

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“…The FRZB polymorphisms have been studied in relation with OA by several investigators. Although they were found to be associated with OA of the lower limbs in some studies [14,16], the results could not be replicated recently in two population-based cohorts [48]. Our analysis was limited by the moderate size of the study population, particularly for subgroup analysis.…”

Section: Discussionmentioning

confidence: 75%

“…However, SFRP3 has been shown to inhibit Wnt signaling in other experimental systems and it has been recently reported that the targeted disruption of the FRZB gene promotes cartilage degradation in mice [10]. On the other hand, some coding polymorphisms of the FRZB gene, which appear to reduce its binding affinity for Wnt, have been associated with knee OA [14,16]. Therefore, further studies are needed to elucidate the actual role of FRZB in the physiology of human bone and cartilage and in the pathogenesis of skeletal disorders.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, it has been suggested that the Wnt pathway may represent a "bone and joint connection" [7]. On the other hand, an association between certain polymorphisms of Wnt-related genes and the risk of OA has been reported [11][12][13][14][15][16]. Those data prompted us to study the expression of an array of Wnt pathway genes in the bone tissue of patients with osteoporotic fractures and OA and to explore the possible differences in the allelic frequencies of a SNP set capturing the common variations of Wnt receptors and inhibitors in both skeletal disorders.…”

Section: Introductionmentioning

confidence: 99%

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Wnt pathway genes in osteoporosis and osteoarthritis: differential expression and genetic association study

et al. 2009

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Section: Discussionmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Wnt pathway genes in osteoporosis and osteoarthritis: differential expression and genetic association study

et al. 2009

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“…A role for the same alleles/ haplotypes in generalized radiographic OA (9) and in hip OA (10) has been reported in other studies in Caucasian populations. Evidence for a differential association of the FRZB R200W single-nucleotide polymorphism (SNP) with hip OA and osteoporosis has been reported (11).…”

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confidence: 99%

Sex and ethnic differences in the association of ASPN, CALM1, COL2A1, COMP, and FRZB with genetic susceptibility to osteoarthritis of the knee

Valdes

Loughlin

Oene

et al. 2007

Arthritis & Rheumatism

180

118

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Objective. To assess whether the association of genetic polymorphisms with osteoarthritis (OA) in other populations could be replicated in a large, multicenter, mixed-sex, case-control study of clinical knee OA.Methods. Genetic polymorphisms in OA candidate genes were genotyped in 298 men and 305 women, ages 50-86 years, all of whom had a diagnosis of knee OA as assessed clinically and radiographically, and in 300 male and 299 female control subjects matched for age and ethnicity. Allele and haplotype frequencies for 5 genes (ASPN, CALM1, COL2A1, COMP, and FRZB) previously tested for association with hip and/or knee OA in other populations were compared between patients and control subjects, analyzing men and women separately.Results. The same FRZB 2-marker single-nucleotide polymorphism (SNP) haplotype associated with hip OA in other populations of Caucasian women was shown to increase the risk of knee OA among the women (but not the men) in the current study (odds ratio [OR] 2.87, P < 0.04). The CALM1 SNP, which affects the risk of hip OA in Japanese individuals, was not shown to be associated with susceptibility to OA in men or women. COL2A1 haplotypes were demonstrated to be associated with a decreased risk of knee OA in men (OR 0.68, P < 0.005) but not in women. COMP haplotypes that were associated with susceptibility to knee OA were different in men and women (P < 0.014 and P < 0.032, respectively). A meta-analysis of these data and those from previously published reports indicated a strong association between the FRZB G324 allele (P < 0.0003) and suggested that an ASPN allele is protective against the risk of knee OA in Caucasians (P < 0.02).Conclusion. 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.

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“…Recently, the Wnt/␤-catenin signaling cascade, which is involved in skeletal and joint development, has received attention in OA (3,4). The potential role of the Wnt signaling pathway in the development of OA has been suggested by the increase in susceptibility for hip OA in women that is associated with 2 functional genetic variants in FRZB, which encodes Frizzled-related protein (FRP) (5)(6)(7)(8). Secreted FRP (sFRP) is a naturally occurring soluble antagonist that competitively binds Wnt to antagonize its ability to signal through Frizzled receptors (9,10).…”

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confidence: 99%

Wnt signaling antagonists are potential prognostic biomarkers for the progression of radiographic hip osteoarthritis in elderly Caucasian women

Lane

Nevitt

Lui

et al. 2007

Arthritis & Rheumatism

117

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Objective. To determine whether serum levels of 2 Wnt signaling antagonists, Frizzled-related protein (FRP) and Dkk-1, are associated with the development and progression of radiographic hip osteoarthritis (RHOA).Methods. Pelvic radiographs were obtained a mean of 8.3 years apart in 5,928 Caucasian women >65 years of age who were enrolled in the Study of Osteoporotic Fractures. Random sampling of this cohort was performed, with ϳ180 subjects per group assigned to 2 nested case-control studies on RHOA incidence and progression. Baseline serum levels of FRP and Dkk-1 were measured by capture enzyme-linked immunosorbent assay. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated using logistic regression analyses with adjustment for potential covariates.Results. There were no differences in serum levels of FRP and Dkk-1 between case subjects with incidence or progression of RHOA and their respective control subjects. There was a trend for higher baseline serum levels of FRP to be associated with a reduced risk of incident RHOA ( Conclusion. Elevated circulating levels of Dkk-1 appeared to be associated with reduced progression of RHOA in elderly women, whereas the highest quartile of serum FRP levels tended to be associated with a modest reduction in risk of incident RHOA.

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Evidence for a differential association of the Arg200Trp single-nucleotide polymorphism in FRZB with hip osteoarthritis and osteoporosis

Cited by 39 publications

References 11 publications

Wnt pathway genes in osteoporosis and osteoarthritis: differential expression and genetic association study

Wnt pathway genes in osteoporosis and osteoarthritis: differential expression and genetic association study

Sex and ethnic differences in the association of ASPN, CALM1, COL2A1, COMP, and FRZB with genetic susceptibility to osteoarthritis of the knee

Wnt signaling antagonists are potential prognostic biomarkers for the progression of radiographic hip osteoarthritis in elderly Caucasian women

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