Tumour necrosis factor-alpha is a proinflammatory cytokine that has been implicated in the propagation of inflammatory responses to bacterial infection and wear debris particles around loosened total hip replacements (THR). Individual TNF responses to such stimuli may be dictated by genetic variation. Single nucleotide polymorphisms (SNPs) at several loci within the TNF gene are associated with disease severity and susceptibility in a number of inflammatory conditions, but only a few SNPs have been screened in any one study.

14 SNPs have been identified within the TNF gene. Our unit has previously demonstrated that 5 SNPs are monomorphic in a sample group of UK Caucasians. We performed a case control study of the remaining 9 polymorphic positions (−1031, −863, −857, −376, −308, −238, +489, +851 and +1304) for possible association with deep sepsis or aseptic loosening.

All patients included in the study were Caucasian and had had a cemented Charnley THR and polyethylene cup. Cases consisted of 44 patients with early aseptic loosening (defined as that occurring within 6 years of implantation and findings at revision surgery or by the criteria of Hodgkinson et al for the acetabulum and Harris for the femoral stem) and 30 patients with microbiological evidence at surgery of deep infection. Controls consisted of 85 THRs that had remained clinically asymptomatic for over 10 years and demonstrated no radiographic features of aseptic loosening or ‘at risk’ signs as described by Wroblewski et al. DNA was extracted from venous blood and genotyped by Snapshot assay.

Genotype and allele frequencies for all SNPs were in Hardy-Weinberg equilibrium between THR controls and a random sample of UK Caucasians. The most significant associations were between the −238A (p< 0.05) and −863T (p< 0.05) alleles and aseptic loosening. A trend towards association was found between the −863A SNP and deep infection (p=0.80). The −238 A/G and −863 G/T genotypes were associated with deep infection (p< 0.05). No other significant associations were found.

Genetic polymorphism of TNF appears to play a significant role in THR aseptic loosening and possibly in deep infection. SNP markers may serve as predictors of implant survival and response to therapy such as anti-TNF treatment.

Dupuytren’s disease is a benign fibroproliferative disease of unknown aetiology. It is often familial and commonly affects Northern European Caucasian men, but genetic studies have yet to identify the relevant genes.

Transforming growth factor beta one (TGF-β1) is a multifunctional cytokine which plays a central role in wound healing and fibrosis. It stimulates the proliferation of fibroblasts and the deposition of extracellular matrix. Previous studies have implicated TGF-β1 in Dupuytren’s disease, suggesting that it may represent a candidate susceptibility gene for this condition.

We have investigated the association of four common single nucleotide polymorphisms in TGF-β1 with the risk of developing Dupuytren’s disease. A polymerase chain reaction-restriction fragment length polymorphism method was used for genotyping TGF-β1 polymorphisms. DNA samples from 135 patients with Dupuytren’s disease and 200 control subjects were examined.

There was no statistically significant difference in TGF-β1 genotype or allele frequency distributions between the patients and controls for the codons 10, 25, −509 and −800 polymorphisms.

Our observations suggest that common TGF-β1 polymorphisms are not associated with a risk of developing Dupuytren’s disease. These data should be interpreted with caution since the lack of association was shown in only one series of patients with only known, common polymorphisms of TGF-β1. To our knowledge, this is the first report of a case-control association study in Dupuytren’s disease using single nucleotide polymorphisms in TGF-β1.