title: Genetic susceptibility to aseptic loosening following total hip arthroplasty: a systematic review.
abstract: Introduction 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.  Source of data We performed a comprehensive search of Medline, CINAHL, Googlescholar, Embase and Cochrane databases, using various combinations of the keyword terms 'aseptic loosening', 'gene', 'hip arthoplasty', 'genetics', 'loosening'. Twelve studies detailing the genetic investigation of patients with aseptic loosening of a THA were identified.  Areas of agreement SNPs of GNAS1, TNF-238 A allele, TNF-α promoter (-308G→A) 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 (29T→C) transitions, A/A genotype for the OPG-163, and MBL were overexpressed in patients with aseptic loosening and periprosthetic osteolysis.  Areas of controversy Data from single centre studies do not allow one to compare the results of different studies.  Conclusion 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.  Growing points 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.  Areas timely for developing research Research in this field could lead to better understanding of mechanisms behind aseptic osteolysis, and improve the results of THA.
authors.affiliation: Department of Orthopaedic and Trauma Surgery, Campus Biomedico University of Rome,Via Alvaro del Portillo, Rome, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Del Buono
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Denaro
authors.forename: Nicola
authors.initials: N
authors.lastname: Maffulli
mesh_terms: D019644:Arthroplasty, Replacement, Hip; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease; D006622:Hip Prosthesis; D006801:Humans; D010014:Osteolysis / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011475:Prosthesis Failure / Q000209:etiology*; D012106:Research