Radiographic osteoarthritis at three joint sites and FRZB, LRP5, and LRP6 polymorphisms in two population-based cohorts

Osteoarthritis Cartilage. 2008 Oct;16(10):1141-9. doi: 10.1016/j.joca.2008.02.007. Epub 2008 Apr 10.


Objective: To examine the association of genetic variation in key players in the Wnt signaling pathway with aspects of osteoarthritis (OA) in two population-based cohort studies: the Rotterdam Study and the Chingford Study.

Methods: Radiographic OA (ROA) was defined as a Kellgren/Lawrence score (K/L) score > or = 2 for the knee and hip. Total hip replacement (THR) was scored. Hand OA was defined as presence of ROA (K/L > or = 2) in two out of three hand joint groups [distal interphalangeal (DIPs), proximal interphalangeal (PIPs), first carpometacarpal (CMC1)/trapezio-scaphoid joint (TS)] of each hand. The concentration of urinary C-terminal cross-linked telopeptide of type II collagen (CTX-II) was standardized to the total urine creatinine. Genotypes for the amino acid variants, Arg200Trp and Arg324Gly of Frizzled-Related protein gene (FRZB), Ala1330Val of Low-density lipoprotein receptor-related protein 5 (LRP5) and Ile1062Val of Low-density lipoprotein receptor-related protein 6 (LRP6), were obtained using the Taqman allelic discrimination assay. A meta-analysis was performed for the FRZB Arg324Gly polymorphism and hip- and knee-OA using RevMan version 4.3.

Results: No consistent associations were observed between the FRZB, LRP5 and LRP6 amino acid variants and radiographic hip-, knee-, or hand-OA or THR, in either study population. While power was limited for most studies to date, a meta-analysis of all published studies regarding the FRZB Arg324Gly polymorphism was performed for hip- and knee-OA separately. This showed no significant associations between the Gly324 allele and risk for hip- or knee OA, although there was large heterogeneity between studies for hip OA in females.

Conclusion: No association was seen between FRZB, LRP5 and LRP6 variants with radiographic osteoarthritic outcomes in two population-based cohorts. In future studies, increased power and standardization of OA-phenotypes are highly recommended for replication studies and to allow meta-analysis.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Female
  • Genetic Predisposition to Disease
  • Glycoproteins / genetics*
  • Glycoproteins / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Joints / metabolism*
  • LDL-Receptor Related Proteins / genetics*
  • LDL-Receptor Related Proteins / metabolism
  • Low Density Lipoprotein Receptor-Related Protein-5
  • Low Density Lipoprotein Receptor-Related Protein-6
  • Male
  • Middle Aged
  • Netherlands / epidemiology
  • Osteoarthritis / diagnostic imaging
  • Osteoarthritis / epidemiology
  • Osteoarthritis / genetics*
  • Polymorphism, Genetic / genetics
  • Radiography
  • Receptors, LDL / genetics*
  • Receptors, LDL / metabolism
  • Signal Transduction / genetics
  • United Kingdom / epidemiology


  • Glycoproteins
  • Intracellular Signaling Peptides and Proteins
  • LDL-Receptor Related Proteins
  • LRP5 protein, human
  • LRP6 protein, human
  • Low Density Lipoprotein Receptor-Related Protein-5
  • Low Density Lipoprotein Receptor-Related Protein-6
  • Receptors, LDL
  • WD repeat containing planar cell polarity effector