Variation in the TNF gene promoter and risk of osteolysis after total hip arthroplasty.
Genetic factors may influence implant failure caused by osteolysis after THA. In an association study of 481 subjects after THA, we found that carriage of the TNF-238A allele was associated with an increased incidence of osteolysis versus noncarriage (odds ratio, 1.7) and was independent of other risk factors. Genetic and environmental factors influence implant survival after THA.


BACKGROUND
Tumor necrosis factor (TNF) is thought to play a role in osteolysis, the major cause of implant failure after total hip arthroplasty (THA). Natural sequence variations at -238 and -308 in the TNF gene promoter are associated with differences in susceptibility to several TNF-mediated diseases. We tested whether these polymorphisms are associated with osteolysis after THA.


METHODS
A total of 481 whites (214 with failed versus 267 with intact implants) were recruited 11.7 +/- 4 years after cemented THA. Genomic DNA was extracted from peripheral blood and genotyped for the -238 and -308 polymorphisms using the Taqman 5' nuclease method. Healthy controls (n = 500) from the background population were also genotyped to establish the local prevalence of these alleles.


RESULTS
The carriage of -238A was 8.8% in the background population and 10.9% in the THA controls (p > 0.05). Carriage of -238A in the osteolysis group was 17.3% (odds ratio, 1.7; 95% CI, 1.0-2.9). Carriage was highest (20.5%) in patients with more widespread osteolysis (OR, 2.1; 1.2-3.8). The association of -238A with osteolysis was independent of other risk factors for osteolysis (logistic regression analysis: OR, 1.8; 1.0-3.2). Carriage of -308A was not associated with osteolysis.


CONCLUSIONS
Genetic, as well as environmental factors, influence implant failure after THA. Whether the TNF-238 polymorphism causes a biological change that predisposes to loosening or is in linkage disequilibrium with such a locus is not yet known.
Wilkinson
J Mark
JM
Division of Clinical Sciences, Bone Metabolism Group, University of Sheffield, Northern General Hospital, Sheffield, United Kingdom. wilkomark@aol.com
Wilson
A Gerard
AG
Stockley
Ian
I
Scott
Ian R
IR
Macdonald
David A
DA
Hamer
Andrew J
AJ
Duff
Gordon W
GW
Eastell
Richard
R
D000368:Aged; D019644:Arthroplasty, Replacement, Hip / Q000009:adverse effects*; D004777:Environment; D005260:Female; D005787:Gene Frequency; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006085:Graft Survival / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010014:Osteolysis / Q000209:etiology / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha