A newly accepted study in The Journal of Arthroplasty describes a genome-wide analysis to identify the genetic loci responsible for implant loosening after total joint arthroplasty. This study was performed as part of the European Union-funded project “HypOrth – New approaches in the development of hypoallergenic implant material in orthopaedics: Steps to personalised medicine,” which is financed under grant agreement 602398. The project was an international effort to understand the mechanisms of the development of aseptic loosening and an applied multidisciplinary approach to achieve this goal.
During the project, variable data were collected, including clinical, genomics, transcriptomics, immunological, microbiological and material data. The international database for revision surgeries containing almost all data collected was developed to support the project. This database allowed researchers to perform complex comparisons and analyze the clinical and biological details of the aseptic loosening (ASL). Two clinical sites recruited patients who had TJA revisions. Other partners performed analysis of the implant material, biosamples and bioinformatics.
The study explored the genetic variants in whole genome scale through genome-wide analysis (GWAS) in patients with ASL compared to the patients without ASL. As a result, several potential single-nucleotide polymorphisms (SNPs) and genomic loci were identified to be involved in ASL and as risk loci for the revision surgery. This study is a first attempt to identify genetic markers for ASL on a genome-wide scale by using a GWAS approach. As a result, researchers identified a clear connection between genetic variability and ASL of TJA implants. This means the risks of patients for developing ASL and requiring revision surgery is dependent on their genetic makeup. The genetic risk for development of ASL that the study identified was substantial and significant. Some discovered genetic variants had the odds ratios greater than 10 to as much as greater than 20. This means the genetic variations determine a large proportion of the risk for ASL and patients with certain genetic alleles have a highly increased risk for revision surgery compared to the controls.
Genetic variations not only predicted the potential need for revision surgery, but they also predicted the survival of the implants, which was defined as the time from primary surgery to the revision. Researchers identified SNPs that were associated more than two-times earlier ASL and earlier revision surgery in patients. For instance, the study identified a SNP associated with the survival of the implant from 8 years (AA variant) to 16 years (GG variant). Interestingly, the heterozygous AG subjects had implant survival of 12 years that is in between the survival times for the homozygous genotypes.
The Cox regression analysis revealed the same SNPs predicted the longevity of the implants and elevated hazard ratios (HR). The highest HR was 19, however other SNPs had a HR of about 4. These numbers illustrate the magnitude of the risk for ASL and to undergo revision surgery after TJA.
Predict likelihood of ASL
This study was important because it used genome-wide screening and identified several new genetic targets that are associated with ASL and predict the likelihood of certain patients to undergo revision earlier than other patients. The results are important for the fundamental research to improve our understanding about the mechanisms of ASL.
On the other hand, by knowing the genetic risk variants, we can identify the patients with increased risk for ASL before primary TJA and, through personalized consulting, we can reduce the need for revision surgery. This is a first step to offer personalized management of patients who undergo TJA to avoid long-term complications and to improve their quality of life. However, additional similar studies are necessary. The authors of the article are looking for colleagues who are interested in collaborating on this work and want to extend the current study by including additional cohorts.
- Koks S, et al. J Arthroplasty. 2019;doi.org/10.1016/j.arth.2019.11.004.
- For more information:
- Sulev Koks, MD, PhD, can be reached Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, 90 South St. Murdoch, Western Australia 6150, Australia; email: email@example.com.
- Christoph H. Lohmann, MD, can be reached at Department of Orthopaedics, Otto-von-Guericke University, Leipziger Str. 44, D-39120 Magdeburg, Germany; email: firstname.lastname@example.org.
- Aare Märtson, MD, PhD, can be reached at Tartu University Hospital, Department/Clinic of Traumatology and Orthopaedics, Puusepa 8, Tartu 51014, Estonia; email: email@example.com.