Variation in the secreted frizzled-related protein-3 gene and risk of osteolysis and heterotopic ossification after total hip arthroplasty.
Secreted frizzled-related protein-3 (sFRP3) antagonizes ligands that promote new bone formation in adult tissues. We examined whether variation in the FRZB gene that encodes sFRP3 is associated with development of osteolysis or heterotopic ossification (HO) after total hip arthroplasty (THA). Genomic DNA was extracted from 609 subjects (osteolysis group n = 268) at a mean of 11 years following cemented THA for idiopathic osteoarthritis and genotyped for the FRZB Arg200Trp and Arg324Gly polymorphisms. The Brooker classification was used to assess HO following primary THA in 563 of the subjects. The carriage rate of the FRZB 200Trp allele was 14.2% in subjects with osteolysis versus 21.0% in controls (p = 0.041). The carriage rate of this allele was 21.7% in subjects with HO (n = 299) versus 12.0% in those without HO (p = 0.063). The odds ratio for osteolysis with carriage of FRZB 200Trp was 0.62 (95% CI 0.38 to 0.99; p = 0.049) and for HO was 1.64 (1.05 to 2.54; p = 0.028), after adjustment for the effects of other risk factors associated with the development of osteolysis or HO. Variants in the FRZB 324 locus alone were not associated with osteolysis or HO. However, the most frequent haplotype (FRZB 200Arg:324Arg) was associated with osteolysis (OR 1.50, 95% CI 1.09 to 2.07; p = 0.014). Our data suggest that the FRZB Arg200Trp locus may be a marker for pro-osteoblastic activity after THA. Carriage of the FRZB 200Trp allele is associated with a "positive" bone balance phenotype (osteolysis -: HO+).
Gordon
Andrew
A
Academic Unit of Bone Metabolism, University of Sheffield, Metabolic Bone Centre, Northern General Hospital, Sheffield, S5 7AU, United Kingdom.
Southam
Lorraine
L
Loughlin
John
J
Wilson
Anthony Gerard
AG
Stockley
Ian
I
Hamer
Andrew J
AJ
Eastell
Richard
R
Wilkinson
Jeremy Mark
JM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009999:Ossification, Heterotopic / Q000209:etiology / Q000235:genetics*; D015207:Osteoarthritis, Hip / Q000601:surgery; D010014:Osteolysis / Q000209:etiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D012307:Risk Factors; D000094742:Secreted Frizzled-Related Proteins
D011506:Proteins; D000094742:Secreted Frizzled-Related Proteins