Genetic susceptibility to total hip replacement failure- Preliminary study on the influence of matrix metalloproteinase-1, interleukin-6 and vitamin D receptor polymorphisms

M HA Malik ^1*, F Jury ², A Bayat ², W ER Ollier ² and P R Kay ³

¹ Arrowe Park Hiospital, Wirral NHS Trust and The University of Manchester, United Kingdom
² CIGMR, University of Manchester, United Kingdom
³ Wrightington Hospital, United Kingdom

^* To whom correspondence should be addressed. E-mail: hammymalik{at}hotmail.com.

Accepted 2 December 2006

Abstract

Matrix metalloproteinase-1 (MMP1), interleukin-6 (IL-6) and vitamin D receptor (VDR) have been implicated in the biological cascade of events initiated by particulate wear debris and bacterial infection resulting in periprosthetic bone loss around loosened total hip replacements (THR). Individual responses to such stimuli may be dictated by genetic variation and we have studied the effect of single nucleotide polymorphisms (SNPs) within these candidate genes. We performed a case-control study of these genes for possible association with deep sepsis or aseptic loosening. All cases were Caucasian patients with osteoarthritis who had received a cemented Charnley THR and polyethylene acetabular cup. Cases consisted of 91 patients with early aseptic loosening and 71 patients with deep infection. Controls consisted of 150 THAs that were clinically asymptomatic for over 10 years and demonstrated no radiographic features of aseptic loosening. DNA samples from all individuals were genotyped using Taqman allelic discrimination. The C allele (p=0.001; OR=3.27; 95% CI 2.21-4.83) and C/C genotype (p=0.001) for the MMP-1 SNP were highly associated with aseptic failure. No such statistically significant relationships were found aseptic loosening and the MMP-2, MMP-4, IL-6 -174 or VDR-L SNPs. The T allele (p=0.007; OR=1.76; 95% CI 1.16 - 2.66) and T/T genotype (p=0.028) for VDR-T were statistically associated with osteolysis due to deep infection. No such other statistically significant relationship was found. Aseptic loosening and possibly deep infection of THR may be under genetic influence and SNP markers may serve as predictors of implant survival and aid pharmacogenomic prevention of THR failure.

Keywords: aseptic loosening, infection, polymorphism, total hip replacement

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