Genetic susceptibility to aseptic loosening following total hip arthroplasty: a systematic review

Aseptic loosening is the most common cause of total hip arthroplasty (THA) failure and revision surgery. Genetic polymorphisms could be determinant factors for implant loosening. We performed a comprehensive search of Medline, CINAHL, Googlescholar, Embase and Cochrane databases, using various combinations of the keyword terms oaseptic loosening', ogene', ohip arthoplasty', ogenetics', oloosening'. Twelve studies detailing the genetic investigation of patients with aseptic loosening of a THA were identified. SNPs of GNAS1, TNF-238 A allele, TNF- promoter (-308GA) transition, IL6-174 G allele, interleukin (IL)-6 (-597) and (-572), MMP-1-promoting gene, C/C genotype for the MMP1, MT1-MMP, MMP-2, transforming growth factor-beta1 signal sequence (29TC) transitions, A/A genotype for the OPG-163, and MBL were overexpressed in patients with aseptic loosening and periprosthetic osteolysis. Data from single centre studies do not allow one to compare the results of different studies. Several gene pathways and genes contribute to the genetic susceptibility to aseptic loosening following THA. Further studies will enhance the understanding of prosthesis failure, and may inform and direct pharmaceutical interventions. Further multi-centre prospective studies are necessary to confirm the general validity of the findings reported. Single-centre findings should be replicated in other centres and populations to open new avenues for pre-surgical genetic testing and to investigate immune response modulation in THA. Research in this field could lead to better understanding of mechanisms behind aseptic osteolysis, and improve the results of THA.