1. “LOSS OF FUNCTION” POLYMORPHISMS OF THE P2RX7 GENE AND PERIPROSTHETIC OSTEOLYSIS AFTER TOTAL HIP ARTHROPLASTY: A PILOT STUDY. Petřek M1, Mrázek F1 , Stahelová A1, Kriegová E1, Gallo J2 1 Laboratory of Immunogenomics and Proteomics, Dept. of Immunology 2 Dept. of Orthopaedics Palacky University and University Hospital Olomouc, Czech Republic
Background
Methods
Periprosthetic osteolysis
Periprosthetic osteolysis (OL) is dominant long-term
complication of the total hip arthroplasty (THA) which can result in prosthetic failure and re-operation.
Pathogenesis of OL is complex – both biological and
mechanical factors play an important role.
Polyethylene wear particles liberated from the prosthetic surfaces stimulate an inflammatory response leading to osteolysis.
Substantial interindividual variability in the severity of OL suggests implication of genetic factors.
P2XR7
Purinergic receptor P2X, ligand-gated ion channel, 7 (P2RX7) is activated by extracellular ATP.
P2RX7 is an important regulator of inflammation and bone turnover, e.g. via effects on osteoclast function and apoptosis.
Several variants of P2RX7 gene with critical effect on P2XR7 expression / function have been described.
Subjects: 205 unrelated Czech patients with cementless type THA - stratified according to the severity of OL (Table 1)
severe OL: N=116
mild/no OL: N=89
2. P2RX7 genotyping
- two selected loss-of-function polymorphisms (Table 2)
- Polymerase Chain Reaction with Sequence Specific Primers (PCR-SSP)
3. Statistics
- conformity of the distribution of genotypes to the Hardy-Weinberg equilibrium
- differences between allelic, genotype and phenotype („carriage rate“) frequencies:
Chi-square test
Hypothesis and Objective
Results
The distribution of P2XR7 genotypes in THA patients corresponded to the H-W equilibrium and to the frequencies observed in Czech and other Caucasian populations (Figure 1).
By comparison with patients with no/mild osteolysis , the uncommon P2RX7 alleles (P2RX7 496Ala / 568Asn) were overrepresented in the patients with severe osteolysis (p>0.05 Figure 2).
Interestingly, rare P2RX7 568Asn allele was found only in patients with THA failure (carriage rate: 0.06) but not in those with functional primary THA (0.00, p=0.09, Figure 3).
Is there any association between the variants of P2RX7 gene and susceptibility to periprosthetic OL/ premature failure after total hip arthroplasty?
Conclusion and Discussion
In this pilot study, the rare P2RX7 568Asn allele tended to be overrepresented in patients with THA failure by comparison with those with functional primary prosthesis.
The limitation of our pilot study is its suboptimal power to demonstrate an association of the rare P2RX7 variant with OL and THA failure. Extension of our preliminary findings in larger THA cohorts is, therefore, warranted. Studies of functionality of P2RX7 polymorphism in this condition are desirable.
Conclusions
Supported by Czech Govt. Funding IGA MZ NR9490 and MSM